Challenges in interpreting gender differences in asthma.
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Adolescent↗
Biomedical subjects
D Gold
Publications and source records attributed to D Gold.
Isn't it time to rethink familial adenomatous polyposis?
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Adenomatous Polyposis Coli↗
Philophthalmus species, probably P. palpebrarum, in Israel: description of the eye fluke from experimental infection.
Following a recent incident of human philophthalmosis in Israel, the intramolluscan larval trematode fauna in snails randomly collected from the suspected water source was checked. Of the snails examined, only Melanopsis praemorsa shed cercariae, including a Philophthalmus cercaria. To identify the philophthalmid species involved, chicks were experimentally infected with metacercariae of the trematode, subsequently yielding mature trematodes resembling those of P. palpebrarum. The majority of trematodes obtained, whether from one-worm infections or from multiple-worm infections resulting in a single trematode in one of the eyes, were relatively small and showed only immature eggs in their uteri. This finding suggests that the existing descriptions of two species of Philophthalmus purportedly harbouring eggs with non-oculate miracidia, namely P. palpebrarum and P. nyrocae, are actually based on immature specimens from one-worm infections that precluded cross-fertilisation. If this be true, then all species of the genus Philophthalmus produce eggs that, when mature, contain oculate miracidia. The species encountered in Israel is thus most likely P. palpebrarum.
Animals↗
Trichomonas vaginalis: strain differences in adhesion to plastic and virulence in vitro and in vivo.
Trichomonas vaginalis isolated from clinical cases were grown axenically in TYI-S-33 medium. Various strains of this flagellate showed different adhesion characteristics in medium containing bovine serum or Cohn fractions thereof. These were not inversely related to the time in axenic culture. The adsorption of serum components to the parasites was assessed in relationship to adhesion but in many cases was probably not adhesion-related. All strains tested for virulence in vitro were almost equally cytotoxic for HeLa tissue cultures. However, in infectivity trials, one of these strains exhibited the highest adhesion capability and proved to be the most virulent for mice, and another (cloned) strain with the poorest adhesion capability failed to cause infection. Other strains exhibited lessened virulence following their extended axenic cultivation. It therefore appears that the in vivo pathogenic potential of the parasites growing in axenic culture is inherently strain-dependent. The findings suggest that although adhesion in whole serum-containing medium is sufficient to differentiate between various Trichomonas isolates, it is insufficiently sensitive to correlate adhesion with virulence. It apparently is important to identify the adhesion-mediating factor(s) in serum or in its Cohn fractions IV-1 and IV-4 and to use it (them) to elucidate the possible correlation between the parasite's capacity to adhere and its pathogenicity.
Adsorption↗
IL-1, TNF-alpha and IL-2 production by peritoneal and spleen cells from Schistosoma mansoni infected mice and its potentiation by preimmunization with schistosomal antigens and immunostimulants.
In the present study we tested the effect of immunization with schistosome derived antigens such as frozen-thawed schistosomula in combination with either BCG, liposomes or liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE), on the resistance of mice to infection, and on the function of their macrophages and lymphocytes. Immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE and subsequent infection, resulted in a 2-3-fold increase in adherent peritoneal macrophage-mediated schistosomulicidal activity (SCA). Peritoneal and spleen macrophages from immunostimulant treated and/or immunized animals showed a significant increase in LPS triggered TNF-alpha production, as compared to non-treated controls. The highest increase in TNF-alpha production was achieved after immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE. LPS triggered IL-1 production was elevated in spleen and peritoneal macrophages from F-T schistosomula + BCG treated mice, and also in spleen macrophages treated with F-T schistosomula + MTP-PE. Only immunization with F-T schistosomula + BCG increased ConA-induced spleen lymphocyte proliferation and IL-2 production. Immunization of mice with F-T schistosomula + BCG also induced protection against parasite infection, while F-T schistosomula + MTP-PE failed to do so. Potentiation of antischistosomal resistance seems to require both macrophage and lymphocyte activation which was achieved only when BCG served as an immunostimulant.
Adjuvants, Immunologic↗
A first instance of human philophthalmosis in Israel.
Conjunctivitis due to the trematode Philophthalmus in a 13-year-old Israeli girl is described. A single worm, probably a mature Philophthalmus palpebrarum, was detected on the palpebral conjunctiva of the upper eyelid of the right eye. Removal of the worm resulted in rapid abatement of the ocular symptoms. This is the first documentation of human philophthalmosis in Israel.
Adolescent↗
The schistosomulicidal activity and the production of IL-1 and TNF-alpha by peritoneal macrophages from infected mice and their potentiation by muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) treatment.
Production of TNF-alpha and IL-1 by adherent peritoneal exudate macrophages (APEM) was monitored for 20 weeks in Schistosoma mansoni infected mice in comparison to their schistosomulicidal activity. LPS-triggered IL-1 and TNF-alpha production by APEM peaked 10 weeks post infection (p.i.) and declined thereafter. The schistosomulicidal activity of APEM also peaked after 10 weeks but remained elevated thereafter. Infected mice were also treated with the immunostimulator liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) 6 or 10 weeks p.i., and their APEM were tested 4 weeks later. APEM from such treated animals showed elevated IL-1 and TNF-alpha production when treatment commenced 6 weeks p.i., while their schistosomulicidal activity increased when treatment commenced either 6 or 10 weeks p.i. The L-arginine inhibitor, NG monomethyl arginine, markedly inhibited the schistosomulicidal activity but not the IL-1 and TNF-alpha production of APEM. Our results show that monokine production increases during the acute phase of infection and declines during its chronic phase, while macrophage schistosomulicidal activity remains constant throughout. Furthermore, TNF-alpha or IL-1 may play a minor role in APEM mediated killing of schistosomula.
Acetylmuramyl-Alanyl-Isoglutamine↗
Differential effects of dunce mutations on associative learning and memory in Drosophila.
Initial learning, 30- and 180-min memory retention after Pavlovian conditioning of an odor avoidance response was quantified in dnc1, dnc2, dncM11 and Canton-S (wild-type) homozygotes and in dnc1/FM7, dnc2/FM7, dncM11/FM7, dncM11/Can-S, Can-S/FM7, dnc1/dncM11 and dnc2/dncM11 heterozygotes. Our results consistently showed that a) the dunce mutations are semi-dominant for initial learning and b) genetic variants carrying the enzymatically hypomorphic dnc2 mutation produce learning scores lower than those of the amorphic dncM11. Analysis of this particular set of retention intervals, using a modified statistical model designed to evaluate decay rates, revealed no discernable effects of the dunce mutations on memory formation 30 to 180 min after training. These results are consistent with a model of memory formation, in which dunce is hypothesized to disrupt acquisition and/or short-term memory.
Animals↗
Human urogenital myiasis due to Eristalis larva: an unusual cause of ureteric obstruction.
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Adult↗
Two distinct pathological syndromes in male CBA/J inbred mice with chronic Schistosoma mansoni infections.
Humans chronically infected with Schistosoma mansoni most commonly present with the relatively asymptomatic intestinal form of the disease, whereas a small minority develop hepatosplenism characterized by severe hepatic disease with portal hypertension. Investigation of hypotheses describing the pathogenic mechanisms underlying the clinical forms of the human disease has been limited by the absence of an animal model that predictably develops such a spectrum of disease. We report that inbred male CBA/J mice that are chronically infected with S. mansoni develop two distinct syndromes, hypersplenomegaly syndrome (HSS) and moderate splenomegaly syndrome (MSS). Pathologically and immunologically, MSS and HSS remarkably parallel the intestinal and hepatosplenic clinical forms, respectively, in humans. HSS affects approximately 20% of these mice and consists of massive splenomegaly, ascites, thymic atrophy, severe anemia, and cachexia. The remaining majority of mice with MSS develop moderate splenomegaly only. Histopathological features of HSS include 1) relatively extensive hepatic fibrosis and granulomatous inflammation, 2) splenic congestion, 3) lymph node plasmacytosis, and 4) worms and eggs in the pulmonary vasculature. Immunologically, the idiotypes present on antisoluble egg antigen antibodies from HSS mice are distinct from those from mice with acute infections or the chronic MSS infection. These idiotypic differences are similar to those observed in patients with intestinal and hepatosplenic forms of the disease and may have regulatory importance. Investigation of the cellular and molecular events that lead to the development of MSS and HSS may advance current understanding of the pathogenesis of the clinical forms of chronic schistosomiasis in humans.
Animals↗
Adhesion of Trichomonas vaginalis to plastic surfaces: requirement for energy and serum constituents.
The ability of Trichomonas vaginalis to adhere to plastic surfaces in the presence of various agents and under different growth conditions was examined in wells of microtitre plates containing unsupplemented TYI medium or the same, with various supplements. Following incubation, the wells were thoroughly washed and adhesion was determined by microscopic counting of the adherent organisms. There was no detectable adhesion in the absence of both serum and carbohydrate. Optimal adhesion (about 10-20% of the total number of parasites) was obtained throughout the growth curve in culture media supplemented with either serum or serum Cohn fractions IV-I (rich in alpha-globulin) or IV-4 (rich in alpha + beta-globulin) and 25 mM glucose, maltose or fructose, but not in plates pre-coated with the Cohn fractions. Cohn fraction II + III (rich in beta + gamma-globulin) moderately enhanced adhesion while Cohn fractions II (rich in gamma-globulin) or V (albumin), fibronectin, Tamm-Horsfall glycoproteins and polylysine were without effect. Non-metabolizable sugars (methyl derivatives of glucose, mannose or fucose) did not support growth, but, surprisingly, enhanced adhesion. At 4 degrees C, the trichomonads were not able to adhere and pre-adherent organisms detached from the plastic surface. Optimal adhesion was obtained at a pH range of 6.5-7.5 but was already detectable at pH 5.5. Cytochalasin E markedly suppressed adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) treatment on mice survival and the generation of schistosomulicidal macrophages.
Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) on the survival of Schistosoma mansoni-infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP-PE showed prolonged survival following either single or repeat infection. The treatment with MTP-PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP-PE treatment significantly reduced granuloma size and markedly diminished liver damaged as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non-treated mice, schistosomulicidal macrophages appeared after 8-10 weeks of infection. In infected mice treated with MTP-PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life-prolonging effects of MTP-PE on S. mansoni-infected mice might indicate an effect of this reagent on cells involved in the granulomatous process.
Acetylmuramyl-Alanyl-Isoglutamine↗
Clonal patterns in the human immune response to HIV-1 infection.
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Animals↗
On the possible schistosomulicidal effect of macrophage-derived lysozyme.
Lysozyme secretion from macrophages of Schistosoma mansoni-infected mice was time dependent, rising significantly from the 8th week post-infection, the macrophages thereafter exhibiting very high levels (greater than 90%) of schistosomulicidal activity. Despite the ability of lysozyme to kill schistosomula in vitro, the concentrations required for such killing were several hundred-fold to several thousand-fold higher than those detected in the supernatants from infected-mice macrophages cultured with or without schistosomula. An in vitro lysozyme inhibitor, N,N,N-triacetyl chitobiose, did not abrogate the cytotoxic ability of macrophages from schistosome-infected mice, but an inhibitor of arginine-dependent cytotoxicity, NG-monomethyl arginine, markedly inhibited schistosomulicidal activity. Evidently, concentrations of ambient lysozyme from macrophage cultures are too low to affect schistosomula in culture, while the main schistosomulicidal pathway in vitro seems to be arginine dependent.
Animals↗
Chronic fatigue in adolescents.
Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.
Adolescent↗
Chronic fatigue. A prospective clinical and virologic study.
To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.
Adult↗
The effect of immunosuppressive and immunostimulatory treatment on experimental amoebiasis.
Immunosuppressive treatments consisting of ionizing irradiation or drugs were employed in inbred and outbred mice and in golden hamsters. Following treatment, mice were challenged intracaecally or intrahepatically with virulent, axenically-grown Entamoeba histolytica. Hamsters were challenged by intraperitoneal injection of the amoebae. Many of the experimental animals died of the combined effects of treatment and challenge. Mice remained essentially refractory to infection with E. histolytica regardless of the immunosuppressive means employed. Liver infection rates in treated and control hamsters were largely similar to one another, i.e. immunosuppressive treatment had no effect on resistance to infection. Our inability to alter the susceptibility of mice and hamsters to amoebic infection by suppressing components of the immune system does not enable us to draw any clearcut conclusions as to the effect of immunosuppression on human amoebiasis. Of the various immunostimulatory materials employed in hamsters, including polysaccharides, BCG and muramyl peptides, only glucan displayed protective capacity against infection with E. histolytica, making it an effective protective agent in an extracellular parasitic infection in addition to its published effectiveness in intracellular protozoal infections. Peritoneal cells extracted from hamsters injected intraperitoneally with E. histolytica seemed capable of reducing the infectivity of virulent amoebae after coincubation in vitro, as shown by reduced infection rates in challenged hamsters. Apparently polymorphonuclear cells, which constituted the vast majority of the extracted cells 24 hours after the stimulatory injection, can, under certain conditions, diminish the infectivity of E. histolytica.
Animals↗
Predictors of asthma and persistent wheeze in a national sample of children in the United States. Association with social class, perinatal events, and race.
This study analyzes data from the Second National Health and Nutritional Examination Survey to determine whether black children are more likely to have asthma or wheeze, even after adjusting for environmental and socioeconomic exposures. For children 6 months to 11 yr of age, the unadjusted prevalence for asthma was 3.0% among white children and 7.2% among blacks; prevalence of frequent wheeze was 6.2% among whites and 9.3% among blacks. In a logistic regression model including race, age, and sex, the relative odds (RO) of asthma for black children as compared to white children were 2.5 (95% confidence interval [Cl], 1.9 to 3.4). Other predictors of asthma in a stepwise logistic regression included age, sex (boys versus girls, RO = 1.4), younger maternal age (2 standard deviation [SD] drop in age, RO = 1.4), residence in the central city (RO = 1.6), and family income (RO for the lowest versus highest tertile, RO = 1.7). After adjusting for these risk factors, age and sex, black children still had a 1.7 RO (95% Cl, 1.2 to 2.1) of having asthma. Frequent wheeze was associated with race (black versus white, RO = 1.6), sex (boys versus girls, RO = 1.3), birth weight (2 SD deficit in birth weight, RO = 1.4), and triceps skinfold thickness (increase in odds of asthma for 2 SD increase in skinfold, RO = 1.6). The significant effect of maternal age and birth weight after adjusting for other confounding variables suggests that the in utero environment may be an important determinant of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Asthma↗