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Biomedical subjects

G J Weil

Publications and source records attributed to G J Weil.

At least 37 records · Page 2Linked to original sources
PubMed1997

Filariasis transmission potential of mosquitoes to humans of different age groups.

Age-specific levels of Wuchereria bancrofti infection determined by microfilaremia in filarious 10 to 60 years old males from endemic village revealed that microfilaria intensity was higher in younger age, presumably because of increased vector biting rate of younger individuals. Out of 1334 Cx. pipiens captured while attempting to bite 51 child-adult bait pairs, 54.0% selected a host in the 10-15 age group. Biting preference towards children was more evaluated (79.2%) later than earlier in the night. Frequency distribution of age-specific biting collections indicated that 62.7% recorded exceeding numbers of bites on children, 21.6% adult biting, and 15.7% equal biting of one of the baits in the pair. Furthermore, 21.6% of the children were exposed to nightly bites ranging from 21 to 64 and only 7.8% of the adults experienced from 21 to 85 bites. Mosquito biting intensity averaged 14.2 and 11.6 bites/night for children and adults respectively. Children experienced 22.4% more bites per night than adults. Thus, children are more exposed to filaria infection and seem to represent an important source of infection. It is concluded that attempts at widespread control of filariasis in the densely populated Nile Delta, where youngsters may account for an immense proportion of the local population, should concentrate on immatures.

Adolescent↗
PubMed1996

Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.

Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected in CD34+CD38+ cells, even in a woman who had her last son 27 years prior to blood sampling. Our data demonstrate the continued maternal circulation of fetal CD34+ or CD34+CD38+ cells from a prior pregnancy. The prolonged persistence of fetal progenitor cells may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus. Pregnancy may thus establish a long-term, low-grade chimeric state in the human female.

ADP-ribosyl Cyclase↗
PubMed1996

Use of recombinant Onchocerca volvulus antigens for diagnosis and surveillance of human onchocerciasis.

The diagnostic value of ELISAs based on recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 was evaluated with sera from endemic areas in West Africa, Guatemala and Ecuador. IgG assays were slightly more sensitive than those that detected IgG4, and the antigen combination was significantly more sensitive than either antigen alone (OC 3.6, 93%; OC 9.3, 84%, combined 98%). These assays were also evaluated with sera from 2 villages in the Onchocerciasis Control Programme area of West Africa including one village (Pendie) with recent recrudescence of infection and one (Niarba) where transmission had been interrupted for 15 years by vector control. The OC 3.6 IgG antibody assay was sensitive for new infections and exposure in Pendie; 24/24 (100%) of people with positive skin snips and 15/74 (20%) of sera from MF negative people had IgG antibodies to this antigen. In addition, antibodies to OC 3.6 often preceded the onset of skin snip positivity in Pendie. In contrast, IgG antibodies to OC 3.6 and OC 9.3 were rarely seen in children born during the 15 years since transmission was interrupted by vector control in Niarba. These encouraging results suggest that antibody assays based on OC 3.6 and OC 9.3 may be valuable tools for surveillance of onchocerciasis and also for monitoring the efficacy of control programmes.

Adolescent↗
PubMed1996

Parasite antigenemia without microfilaremia in bancroftian filariasis.

The term "endemic normal" in the context of filariasis refers to people who are amicrofilaremic and free of clinical signs or symptoms of filariasis despite regular exposure to the parasite. Some sera from endemic normals contain soluble Wuchereria bancrofti antigens that are detectable by enzyme-linked immunosorbent assay. We now report evidence that filarial antigenemia in these people is not an artifact and that it is indicative of active W. bancrofti infection. Filarial antigenemia was first detected within one month of the onset of microfilarial patency in experimentally infected primates. Human sera from antigen-positive endemic normals contained the same filarial antigens (by Western blot) as sera from people with microfilaremia. Sera from antigen-positive endemic normals also contained significantly higher levels of immunoglobulin G4 antibodies to native and recombinant filarial antigens than sera from antigen-negative controls matched for age and sex. The epidemiology of filarial antigenemia in endemic normals was studied with sera from a population-based study of filariasis in an Egyptian village with a microfilaria prevalence of 29%. Seventeen percent of endemic normals had antigenemia, and this group comprised 11% of the total village sample. Filarial antigenemia was significantly more common in endemic normals more than 30 years of age than in younger people. These results suggest that amicrofilaremic and asymptomatic W. bancrofti infections are relatively common in endemic areas. Additional studies are needed to determine the clinical significance, prognosis, and optimal management of such infections.

Adolescent↗
PubMed1995

Neutrophil functional responses depend on immune complex valency.

Ligand-induced cross-linking of Fc gamma receptors (Fc gamma R) on neutrophils plays a significant role in their stimulation, shown here by contrasting the responses induced by low valency immune complexes (LICs) and high valency immune complexes (HICs) and by cross-linking LICs in situ (L/Ab) after their addition to the cells. Multiparameter flow cytometry was used to measure immune complex (IC)-elicited changes in cytoplasmic Ca2+ concentration and initiation of the oxidative burst simultaneously in the same cell and to correlate these with Fc gamma R occupancy. We have previously shown that subpopulations of neutrophils respond maximally to subsaturating concentrations of HIC; saturating dosages stimulate the entire population. This discrepancy was not due to differences in receptor occupancy. The magnitude of the transient Ca2+ increase was independent of the dose of HIC but depended on the dose when an LIC was used. As shown here, L/Ab cross-linking elicited Ca2+ responses similar to those observed in HIC-stimulated cells. In contrast, LIC elicited only minimal intracellular delta pH and no oxidative burst or membrane potential changes at all unless Fc gamma R was cross-linked, accomplished by HIC or by L/Ab. However, azurophilic degranulation, as determined by elastase release, was not observed in cells stimulated by the in situ cross-linking method, whereas the HIC preparation triggered azurophilic degranulation. Thus, some Fc gamma R-mediated neutrophil effector functions such as azurophilic degranulation and oxidative burst initiation have an absolute requirement for Fc gamma R cross-linking, whereas signaling functions such as changes in membrane potential, intracellular pH, and intracellular Ca2+ concentration can occur, albeit more slowly and to a lesser extent, if single Fc gamma R are occupied.

Amiloride↗
PubMed1995

Onchocerca volvulus: parasitologic and serologic responses in experimentally infected chimpanzees and mangabey monkeys.

Six chimpanzees (Pan troglodytes) and six mangabey monkeys (Cercocebus atys) were inoculated with Onchocerca volvulus third-stage larvae (L3) of West African origin. Two chimpanzees each received 200, 300, or 400 L3, while three mangabeys each received either 50 or 250 L3. All six chimpanzees became microfilaria positive between 11 and 25 months postinoculation (PI), while two of the six mangabeys were skin-snip positive at 24 and 37 months PI, respectively. All chimpanzees developed antibodies to two native antigens of 14 and 22 kDa and to the recombinant antigens OV16, OC3.6, and OC9.3. Marked antibody responses were observed in the mangabey monkeys, and in general, the responses were similar to those observed in the chimpanzees. However, in the mangabeys, these responses did not generally manifest themselves until later in the infection. The results of this study suggest that in chimpanzees, the smallest inoculum used, 200 L3, was sufficient to initiate consistent infections that had parasitologic and immunologic parameters equivalent to animals inoculated with larger numbers of larvae. Similarly, inoculation of mangabey monkeys with small numbers of larvae appeared to be as likely to establish infection and induce immunologic responses as did inoculation of larger numbers of larvae. Microfilaria-positive chimpanzees and mangabey monkeys were examined by three conventional imaging techniques (X ray, ultrasound, and magnetic resonance imaging (MRI)), but no adult worms or nodules could be identified in any animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cloning of an early immunodominant filarial antigen: a member of the Brugia malayi myosin heavy chain gene family.

Partial protective immunity to filariasis can be achieved in animals by vaccination with irradiated infective larvae. A Brugia malayi cDNA expression library was screened with serum pools from vaccinated and infected jirds to select clones that expressed potentially protective recombinant antigens that were preferentially recognized by sera from vaccinated animals. Bmmyo-2, the largest of a group of related clones, was studied in detail. Jirds produced strong antibody responses to the protein product of Bmmyo-2, Bmmhc-B, as early as 1 month after vaccination with irradiated larvae. Antibody responses to Bmmhc-B in infected jirds were weaker than those of vaccinated jirds, and they developed somewhat later. Antibodies produced to Bmmhc-B were reactive with a 200 kDa native B. malayi antigen by immunoblot and with muscle bands in the body wall of microfilarial by indirect immunofluorescence. Sequence analysis of the 1454 bp cDNA insert of Bmmyo-2 showed that it codes for a portion of the rod region of a B. malayi myosin heavy chain isoform. The deduced amino acid sequence of Bmmyo-2 is 74.6% identical with that of the corresponding region of Caenorhabditis elegans myosin heavy chain B, but only 64.6% identical with a recently described B. malayi myosin heavy chain, Bmmhc-A.

Amino Acid Sequence↗
PubMed1995

Effect of ivermectin prophylaxis on antibody responses to Onchocerca volvulus recombinant antigens in experimentally infected chimpanzees.

Antibody responses to recombinant Onchocerca volvulus antigens were studied in experimentally infected chimpanzees. Sera from 3 groups of 6 animals were tested by ELISA with recombinant antigens OC 3.6 and OC 9.3. Groups I and II were treated with 200 micrograms/kg of ivermectin on the day of infection or on day 28, respectively. Group III were untreated controls. Antibodies to OC 3.6 developed during the prepatent period in all 3 groups. In contrast, antibodies to OC 9.3 were usually first detected around the time of onset of patency. Several animals had early antibody responses to OC 9.3, but these animals subsequently failed to develop microfilarial patency. Only 1 of 6 animals in group I produced a strong antibody response to OC 9.3 while all 12 animals in groups II and III developed antibodies to this antigen. Although there was some inconsistency in antibody responses observed in each treatment group, the results suggest that OC 9.3 may be more useful than OC 3.6 for monitoring the efficacy of prophylactic drugs or vaccines for onchocerciasis while OC 3.6 may be useful for detecting exposure to the parasite and early infection, regardless of the later outcome of the infection.

Animals↗
PubMed1995

Molecular characterization of a Brugia malayi intermediate filament protein which is an excretory-secretory product of adult worms.

Filarial parasites release macromolecules into their environment both in vitro and in vivo. These excretory-secretory products (E-S) have been studied with respect to function, vaccination potential, pathogenicity, and ability to serve as antigen targets for diagnostic tests. We have recently described monoclonal antibody OV-1 which binds to an intermediate filament in E-S and circulating antigens of Onchocerca volvulus. OV-1 also binds to cross-reactive antigens of Brugia malayi. Therefore, OV-1 was used to immunoscreen a B. malayi adult worm cDNA library in an attempt to clone a homologue (BMIF). BMIF is a 1664-bp full-length transcript which codes for 505 amino acids. BMIF has 95% sequence homology at the amino-acid level to OV1CF, an O. volvulus intermediate filament that was also selected with OV-1, and 75% homology to Ascaris intermediate filament A. Southern blot analysis suggests that BMIF is confined to a single location in the genomic DNA of B. malayi. Antibodies raised to BMIF identified native antigens in immunoblots of B. malayi adult worms, infective larvae and adult E-S. In addition, the antibody also bound to a 60-kDa antigen in immunoblots of poly(ethylene glycol)-precipitated immune complexes in sera from B. malayi infected patients. Localization studies showed that the antigen encoded by BMIF is present in the hypodermis, developing embryos and muscle of adult B. malayi. These studies show that BMIF is an E-S product of B. malayi adult worms which is detectable in sera from patients with brugian filariasis.

Amino Acid Sequence↗
PubMed1995

Molecular characterization of a parasite antigen in sera from onchocerciasis patients that is immunologically cross-reactive with human keratin.

Onchocerca volvulus is a nematode that causes severe dermatitis and blindness in humans. Prior studies have shown that immune complexes in sera from onchocerciasis patients contain parasite antigens with M(r) of 23,000 and 65,000-70,000. Monoclonal antibody OV-1 binds to these antigens and to corresponding antigens in adult worm extracts and in vitro culture supernatants. OV-1 was used to immunoscreen an O. volvulus adult worm cDNA library. Clone OV1CF contains a 1632-bp open-reading frame that codes for a protein with a predicted M(r) of 63,000. The deduced protein sequence of OV1CF has 78% identity with Ascaris lumbricoides intermediate filament A and 40%-50% identity with several mammalian intermediate filaments. Antibodies raised to OV1CF bind to human keratin, and some sera from onchocerciasis patients contain antibodies to OV1CF and to keratin. Thus, immune complexes from onchocerciasis patients contain a parasite antigen that is immunologically cross-reactive with human intermediate filament proteins.

Adolescent↗
PubMed1995

Clearance of circulating filarial antigen as a measure of the macrofilaricidal activity of diethylcarbamazine in Wuchereria bancrofti infection.

Small doses of diethylcarbamazine (DEC) clear microfilariae (MF) from the blood of Wuchereria bancrofti-infected persons, but the dose and regimen required to kill adult worms is not clearly defined. A prospective study was undertaken to examine the macrofilaricidal effect of DEC and the ability of an assay for circulating filarial antigen (CFA) to define the effect. Twenty-five MF-positive subjects and 7 MF-negative but CFA-positive subjects were treated with DEC and followed for 18 months. Of the 25 MF-positive patients, 24 cleared MF, and 22 of 26 CFA-positive subjects cleared CFA. A significantly greater decrease in antifilarial IgG4 was seen in patients who cleared CFA than in those who did not. The complete clearance of CFA observed after therapy with DEC indicates that assessment of CFA clearance is a useful means for detecting macrofilaricidal effects of antifilarial chemotherapy.

Adolescent↗
PubMed1995

Combination ivermectin plus diethylcarbamazine, a new effective tool for control of lymphatic filariasis.

In 1993, a three arm double-blind controlled trial was implemented in French Polynesia, to compare the tolerance and efficacy of single doses of the combination ivermectin (IVR) 400 micrograms.kg-1 plus diethylcarbamazine (DEC) 6mg.kg-1 vs IVR 400 micrograms.kg-1 or DEC 6 mg.kg-1 alone, for treatment of Wuchereria bancrofti carriers. Of the 57 treated male patients in whom microfilaremia (mf) densities ranged from 22 to 4,709 mf/ml, three groups of 19 were randomly selected, and allocated to one of the three treatments. Twelve months after treatment 37%, 16% and 16% of patients were mf negative in groups DEC, IVR and IVR plus DEC respectively. Mf percent return to pretreatment level was significantly lower in the group IVR + DEC (1.9%) than for DEC 6 (14.7%) or IVR 400 (11.6%). Antigenemia percent return to pretreatment level was lower in the groups IVR + DEC or DEC 6 than for IVR 400. The combination IVR + DEC proved to be the most effective on macrofilariae and microfilariae (antigenemia and mf negative patients). The combination will be a very powerful tool for control of lymphatic filariasis. An annual filariasis day could be the most cost-effective strategy for administration of the drugs.

Animals↗
PubMed1994

Molecular cloning of Brugia malayi antigens for diagnosis of lymphatic filariasis.

Immunological crossreactivity among nematodes has hampered development of specific serodiagnostic assays for lymphatic filariasis. In the present study, we report the molecular cloning and characterization of two filaria-specific recombinant clones (BmM5 and BmM14) with immunodiagnostic potential. BmM5 is a 505-bp cDNA which codes for a protein of 130 residues that ends with an endoplasmic reticulum targeting sequence. BmM14 is closely related to a recently reported clone (SXP-1), and it has 62% homology (deduced amino acid sequence) with a previously described Onchocerca volvulus clone, lambda RAL-2. Glutathione S-transferase fusion proteins of BmM5 and BmM14 were tested in various ELISA formats. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. ELISA studies showed that approximately 90% of 111 sera from Indian and Egyptian patients with brugian and bancroftian filariasis were reactive with both antigens. Nonendemic sera as well as sera from patients with schistosomiasis or intestinal helminths were uniformly nonreactive. Assays based on BmM5 and BmM14 may be useful for large scale screening as an alternative to microfilaria or filarial antigen detection as a means of obtaining a rough index of filariasis endemicity in previously unstudied areas.

Amino Acid Sequence↗
PubMed1993

Vaccination with recombinant filarial paramyosin induces partial immunity to Brugia malayi infection in jirds.

Vaccination with irradiated infective larvae induces partial protective immunity to infection with the filarial nematode Brugia malayi in jirds. Prior studies have shown that such immunization stimulates a much stronger antibody response to recombinant and native filarial paramyosin than that seen after normal infection. To determine whether vaccination with recombinant paramyosin could induce protective immunity to larval challenge, jirds were immunized with either B. malayi paramyosin and maltose binding protein (BM5-MBP) (fusion protein of B. malayi paramyosin and maltose-binding protein), MBP alone, or recombinant Dirofilaria immitis paramyosin. Animals were challenged with 100 infective larvae s.c. 8 wk after the second immunization. Necropsies were performed 16 wk after challenge. Vaccination with BM5-MBP induced significant protective immunity; adult worm recoveries, worm lengths, and blood microfilaria counts were reduced in the BM5-MBP group relative to the MBP control group. The reductions in adult worm recoveries (43%) and female worm lengths (10%) were statistically significant (p < 0.05). Interestingly, protective immunity was not induced by immunization with D. immitis paramyosin. Additional studies are needed to identify mechanisms involved in protective immunity induced by BM5-MBP and to understand the differential activity of the two closely related recombinant paramyosin proteins in this model.

Animals↗
PubMed1993

Onchocerca volvulus: monoclonal antibodies to immune complex-associated parasite antigens.

Improved methods for diagnosis of onchocerciasis are needed. We have recently identified immune complex-associated parasite antigens in sera from onchocerciasis patients. The goal of this study was to produce monoclonal antibodies to these antigens that might be used in antigen detection assays. Two monoclonal antibodies (OV-1 and OV-5) that bind to parasite antigens in immunoblots of PEG-precipitated immune complexes from human onchocerciasis sera and to corresponding antigens in adult worm extracts and excretory-secretory products were produced. The target epitopes of the monoclonals are heat stable, resistant to trypsin, and destroyed by Pronase. The two monoclonals produce similar but not identical patterns of binding to immunoblots of Onchocerca volvulus adult worm antigen with major bands at 43-47, 58-63, and 70 kDa. OV-1 and OV-5 appear to bind to two distinct but closely related epitopes, neither of which is phosphorylcholine. Immunoelectron microscopy showed that the epitopes recognized by these monoclonals are widely distributed in adult female worms, but concentrated in the uterus and intestine. Antigen assays based on these antibodies detected parasite antigen in 9 of 14 sera from onchocerciasis patients, but significant background signal was detected in some nonendemic human sera. Thus, although this study has provided new information on parasite antigens in sera from onchocerciasis patients, additional work will be needed to achieve the goal of producing a sensitive and specific antigen diagnostic test for onchocerciasis.

Animals↗
PubMed1993

Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome.

OBJECTIVE: To describe clinical and laboratory features of patients with severe ehrlichiosis, some of whom presented with toxic shock syndrome (TSS)-like illnesses, and to report, to our knowledge, the first documented fatal case of ehrlichiosis in a child. DESIGN: Case series. SETTING: Tertiary-care medical center. PATIENTS: All patients with documented ehrlichiosis during a 3-year period, August 1, 1989, to July 31, 1992. RESULTS: Eight patients (age range: 2 to 46 years) met clinical and serologic diagnostic criteria for ehrlichiosis. The mean interval from first contact with a physician to initiation of appropriate antibiotic therapy was 4.6 days (range: 1 to 11 days). All eight patients with ehrlichiosis had fever, chills, thrombocytopenia, and abnormal liver function test results. Most patients also had rash (seven), conjunctival hemorrhage or erythema (six), and leukopenia (six). Four cases met diagnostic criteria for TSS with fever, hypotension, rash, and multiorgan dysfunction. Two patients required mechanical ventilation, and one of these, a 6 1/2-year-old boy, died of complications of the infection. A ninth patient with probable ehrlichiosis also met diagnostic criteria for TSS. CONCLUSIONS: Human ehrlichiosis can present as a severe, life-threatening illness that may resemble TSS. The diagnosis of ehrlichiosis was not considered by the physicians who first cared for these patients. Greater awareness of the potential severity of ehrlichiosis is needed to ensure that proper treatment is initiated early in the course of the disease.

Adolescent↗
PubMed1993

Preliminary evaluation of recombinant Onchocerca volvulus antigens for serodiagnosis of onchocerciasis.

Serodiagnostic assays for onchocerciasis based on native antigens are hampered by the scarcity of antigen, and they suffer from poor specificity. The present study was designed to evaluate the diagnostic utility of recently described recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 in enzyme immunoassays. The recombinant proteins were expressed as glutathione S-transferase fusions and were tested in several enzyme immunoassay formats to measure immunoglobulin G (IgG) and IgG4 antibodies with sera from patients with onchocerciasis in Nigeria and with various types of control sera. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. Forty of 42 (95%) serum specimens from patients with onchocerciasis were reactive with OC 3.6; the reactivity with OC 9.3 was 81%. Results obtained with sera from experimentally infected chimpanzees suggest that OC 3.6 might be especially useful for detecting prepatent infections in humans, while OC 9.3 mainly detects mature, patent infections. Sera from individuals in Nigeria and the United States residing in areas nonendemic for onchocerciasis were uniformly nonreactive with these antigens in IgG and IgG4 assays, as were sera from patients with bancroftian filariasis, brugian filariasis, loiasis, ascariasis, schistomiasis, and dracunculiasis. These results suggest that enzyme immunoassays based on the recombinant antigens OC 3.6 and OC 9.3 are useful for the diagnosis of onchocerciasis.

Animals↗