A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils.

IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure.

Anti-melanin antibodies are increased in sera in Parkinson's disease.

An increasing body of research suggests that a number of immune mechanisms play a role in degenerative pathways in Parkinson's disease (PD). In the current work we investigated a posited humoral immune response in this disorder. Sera from PD patients exhibited a significantly enhanced absorbance response on a novel ELISA for anti-melanin antibodies, compared to sera from age-matched control subjects. The enhanced ELISA absorbance response was specific for catecholamine-based melanins and was unrelated to antiparkinsonian dopaminergic medication. Further, the absorbance response was significantly and negatively correlated with disease duration. These data suggest that a specific humoral anti-melanin antibody response is present in PD and is more active in early disease. While the contribution of this novel immune response to the initiation and progression of this disorder is unclear, this finding supports the hypothesis that specific immune responses occurring in PD may respond to therapeutic interventions in this disorder.

Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis.

In sub-Saharan Africa, chronic hepatosplenomegaly, with palpable firm/hard organ consistency, is common, particularly among school-aged children. This morbidity can be caused by long-term exposure to malaria, or by Schistosoma mansoni, and it is exacerbated when these two occur together. Although immunological mechanisms probably underlie the pathogenic process, these mechanisms have not been identified, nor is it known whether the two parasites augment the same mechanisms or induce unrelated processes that nonetheless have additive or synergistic effects. Kenyan primary schoolchildren, living in a malaria/schistosomiasis co-transmission area, participated in cross-sectional parasitological and clinical studies in which circulating immune modulator levels were also measured. Plasma IL-12p70, sTNF-RII, IL-10 and IL-13 levels correlated with relative exposure to malaria, and with hepatosplenomegaly. Soluble-TNF-RII and IL-10 were higher in children infected with S. mansoni. Hepatosplenomegaly caused by chronic exposure to malaria was clearly associated with increased circulating levels of pro-inflammatory mediators, with higher levels of regulatory modulators, and with tissue repair cytokines, perhaps being required to control the inflammatory response. The higher levels of regulatory modulators amongst S. mansoni infected children, compared to those without detectable S. mansoni and malarial infections, but exposed to malaria, suggest that S. mansoni infection may augment the underlying inflammatory reaction.

Characterization of immunoglobulin binding by schistosomes.

Although controversial, schistosomes are believed to cloak themselves in antibody through non-specific interactions with the immunoglobulin (Ig) molecule. The acquisition of host Ig by the schistosome may mask its foreign status and/or interfere with Fc-dependent functions. We report experiments aimed at characterizing the interaction between Ig-Fc and paramyosin, a schistosome Fc-receptor previously reported to bind human IgG. We show that certain Ig classes, in particular murine IgG2b and IgG3, are not only able to bind recombinant paramyosin, but also associate with other parasite proteins. The Fc region of IgG contains four hydrophobic patches, two of which are known to interact with distinct molecules: one in the Cgamma2-Cgamma3 interdomain region bound by protein G, mannose binding lectin (MBL), and the neonatal Fc-receptor (FcRn), and one at the top of the Cgamma2 domain bound by phagocytic FcgammaRs and C1q. We provisionally discounted the involvement of these regions, since IgG binding by paramyosin did not inhibit FcgammaR-mediated NADPH respiratory bursts, and protein G was unable to block IgG binding to paramyosin. Given their apparent low affinity, we postulate hydrogen bonding between reactive residues in a hydrophobic patch at the bottom of the Cgamma3 domain and negatively charged Glu or Asp amino acids in paramyosin.

Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice.

The spontaneous development of insulin dependent diabetes mellitus in non-obese diabetic (NOD) mice has been shown to be mediated by a Th1 response against beta cell antigens. It is known that in murine models of Schistosoma mansoni infection, egg production is associated with a switch from a Th1 to Th2 response. This subsequent dominance of a Th2 response in S.mansoni infected mice has been shown to influence the response to other infectious agents or antigens. We therefore determined whether infection with S.mansoni could influence the spontaneous incidence of insulin dependent diabetes mellitus (IDDM) in NOD mice. Infection with this helminth significantly reduced the spontaneous incidence of IDDM. IDDM was also prevented by injecting parasite eggs alone. Because until relatively recently humans might expect to succumb to a variety of infectious agents, the current freedom from infection might permit the expression of a genetic predisposition to autoimmune pathology and be responsible for the increased incidence of IDDM.

Dehydroepiandrosterone sulfate treatment of mice modulates infection with Schistosoma mansoni.

Female mice treated with dehydroepiandrosterone sulfate early during infection were partially protected (P < 0.05-0.005) from Schistosoma mansoni infection. Hormone treatment did not modify parasite-specific cellular or humoral responses. Serum dehydroepiandrosterone sulfate levels and testosterone infection were negatively correlated, r = -0.621 and r = -0.653, respectively, with schistosome worm burden. The partial resistance to schistosome infection in dehydroepiandrosterone sulfate-treated female mice may be due to the known antischistosomular activity of testosterone.

High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.

In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.

Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition.

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non-attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate-sensitive and -resistant epitopes in 'skin-stage', 'lung-stage' and 'liver-stage' schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species-specific responses, and vaccination-specific responses were examined. No response developed in parallel with serum-mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non-protective CIS.

Ultrastructure of the olfactory organ of the newt, Cynops pyrrhogaster.

The ultrastructure of the nasal sacs of the Japanese newt, Cynops pyrrhogaster, was studied by scanning and transmission electron microscopy. The paired nasal sacs of the newt are dorsoventrally flattened with a lateral nasal sinus off the main cavity of each sac. Throughout each sac is a series of ridges and grooves. In the main cavity, sensory epithelium with ciliated and microvillous receptor cells lines the grooves, and a thin, ciliated non-sensory epithelium lines the ridges. Secretory glands are present in the lamina propria. In the lateral nasal sinus, the ridges are lined with a thick, non-ciliated sensory epithelium that lacks glands. This region resembles and may function as a primitive vomeronasal organ.

Epidermal lipid in several cetacean species: ultrastructural observations.

The ultrastructure of the skin of four cetacean species, bottlenose dolphin (Tursiops truncatus) long-finned pilot whale (Globicephala melaena), humpback whale (Megaptera novaeangliae), and fin whale (Balaenoptera physalus) was investigated with particular reference to epidermal lipid. It has already been established that massive lipid reservoirs exist in whales, that the biochemical structures of cetacean lipids are unique, and that unusual intracellular lipid droplets appear in the epidermis. We report here some novel findings on scanning electron microscopic morphology of epidermal lipid, and on its ultrastructural morphology in general and specialized integumentary sites, including species not previously investigated. The intracellular epidermal lipid droplets were more extensive than lamellar body-derived intercellular lipid which is within the interstices of stratum externum cells. The intracellular droplets were spherical, highly variable in size ranging from 0.24 micron to 3.0 microns in diameter, appeared singly or were aggregated in cytoplasmic cavitations, and often were closely associated with epidermal cell nuclei. Evidence for exocytosis of the intracellular droplets was not observed. Significant numbers of intracellular lipid droplets are not observed in the epidermis of terrestrial mammals, so their presence is one of several aquatic specializations of the cetacean integument. Its full significance remains obscure, but it is more probably associated with epidermal cell metabolism than with secretion of lipid.

The use of mouse/human chimaeric antibodies to investigate the roles of different antibody isotypes, including IgA2, in the killing of Schistosoma mansoni schistosomula by eosinophils.

We report the use of a matched set of mice/human chimaeric antibodies, directed against the 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody-mediated eosinophil-dependent killing of schistosomula. The chimaeric antibodies consist of mouse VH, VL and CL regions with human gamma 1, gamma 2, gamma 3 (2 allotypes), gamma 4, alpha 2, mu or epsilon CH regions and were used in in vitro assays with human eosinophils and NIP-coated S. mansoni schistosomula. Some anti-NIP isotypes mediated high levels of killing, which was specific for NIP-coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti-schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.

Perceptions of risk factors related to cancer, venereal diseases and AIDS among adult Barbadians - abstract

As part of a knowledge, attitudes, practices and beliefs (KAPB) survey, in relation to AIDS among the adult population in Barbados, questions were asked that sought to gain insight into the population's perceptions of risk factors, and the level of fear related to cancer, venereal diseases and AIDS. Public education by a variety of organizations in Barbados has sought to raise the awareness of the public about AIDS and cancer. The KAPB survey was carried out by trained interviewers, using a structured pretested questionaire, on a sample of the population derived in a systematic manner from the electoral register. The 509 respondents represent 0.2 percent of the population of Barbados. Ninety-five point seven per cent (95.7 percent) of respondents recognised smoking as an increased risk for cancer. Nearly eighty per cent of respondents felt that a person's lifestyle could prevent getting veneral diseases (78.8 percent) and AIDS (79.6 percent), whilst only 36.9 per cent felt that lifestyle could prevent a person getting cancer. The responses about lifestyle were reflected in the personal responsibility respondents felt if they got these illnesses. More males (45 percent) than females (29.9 percent), and those in younger age groups, felt that lifestyle was responsible for getting cancer. However, there were no age or gender differences in the perceptions of lifestyle and acquiring AIDS or venereal diseases. The older age group (55 - 64 years) was less scared of getting cancer, VD or AIDS, and although differences were small, men (45.4 percent) were less scared than women (38.2 percent) of getting cancer, and women (37.5 percent) less scared than men (34 percent) of getting AIDS(AU)

Risk factors for cardiovascular disease knowledge and beliefs of the Barbadian population - abstract

A knowledge, attitudes and practices survey in relation to cardioascular disease in Barbados was carried out by a questionaire administered to a 0.2 per cent representative sample of the Barbadian population. A section of the questionaire dealt with knowledge and beliefs of cardiovascular disease and its risk factors. Analysis of the responses showed that knowledge of the part played by smoking, obesity, exercise, and worry in the development of cardiovascular disease was good, with between 81 and 92 percent being aware of these. Many responders were also aware of diabetes (62 percent), regular taking of aspirin (65 percent) and eating fish (70 percent) and their relationship to heart disease, its development or prevention. At a personal level, less than half of the respondents thought their lifestyle could prevent getting a heart attack (41 percent), a stroke (39.5 percent), or diabetes mellitus (39.7 percent). As a group, the respondents claimed that they got regular exercise. However, the number of those claiming this was smaller in the age group 35 - 44 years - 25 per cent. The results show the success of work done in public health education, and identify areas such as transforming knowledge into lifestyle change, where success must be achieved (AU)

The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (alpha 1 and omega 1) from Schistosoma mansoni eggs.

T cell-deprived mice acutely infected with S. mansoni suffer microvesicular hepatocyte damage which is not seen in infected, immunological intact animals. A cationic fraction (CEF6) of the PBS-soluble portion of S. mansoni eggs (SEA) induces antibodies which, on passive transfer, prevent hepatocyte damage. CEF6 contains 2 antigens, omega 1 and alpha 1, and has also been shown to be a useful serodiagnostic reagent. This paper describes the purification and characterization of the 2 antigens present in CEF6. omega 1 is a monomeric glycoprotein with a pI greater than 9.0 and a molecular weight of 31 kDa. Alpha 1 consists of two immunologically cross-reactive dimers, 41 and 36 kDa in non-reducing conditions, each of which consists of one unique and one common glycoprotein subcomponent. In ELISA with mouse and human infection sera omega 1 is shown to be S. mansoni specific and is better able to distinguish S. mansoni infections from other schistosome infections than are unfractionated SEA, CEF6 or alpha 1. Passive transfer of monospecific anti-omega 1 sera into S. mansoni infected, T cell-deprived mice completely prevented the occurrence of microvesicular hepatocyte damage in these animals. Monospecific anti-alpha 1 serum had no hepatoprotective capacity.

Cooperative state-federal turkey ornithosis task force, Texas, 1974.

Ornithosis was suggested by a routine analysis of tissue specimens from Texas turkey flocks submitted to the Texas A&M University Poultry Disease Laboratory at Gonzales on April 30, 1974, and of subsequent specimens from four additional flocks. Subsequently, illness in humans at turkey processing plants in Texas, Nebraska, and Missouri, implicating turkeys from Texas, was confirmed as ornithosis in July 1974; and, associated with this outbreak, ornithosis was suspected as the cause of the death of one human. Action was taken by state and federal poultry disease control and inspection officials, public health agencies, and the turkey industry in Texas.