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Biomedical subjects

J B Lok

Publications and source records attributed to J B Lok.

At least 19 recordsLinked to original sources
PubMed1996

Strongyloides stercoralis: maintenance of exceedingly chronic infections.

Two hypotheses were tested to identify the mechanism(s) by which chronic Strongyloides stercoralis infections are maintained in experimental dogs as a model to explain delayed onset recrudescence in humans. Investigations tested the hypotheses that chronic infections result from 1) periodic reactivation of third-stage larvae from a reservoir of dormant parasites outside the gastrointestinal tract or 2) the periodic rejuvenation of postreproductive female worms remaining from a previous infection, lodged in the mucosal crypts. Populations of parenteral larvae survived in mature experimentally infected female dogs for 66 days; individual worms survived for 88 days, but there was no evidence that these larvae re-established patent, adult worm infections. Late in these infections, female worms were present in greater than predicted numbers with no evidence that autoinfection had occurred, suggesting that some postreproductive worms were long-lived. In separate trials, long-lived spent females were once again capable of producing viable larvae when the host was treated with corticosteroids.

Animals↗
PubMed1995

Studies of reproductive competence in male Dirofilaria immitis treated with milbemycin oxime.

Normal adult Dirofilaria immitis from a microfilaremic donor dog and D. immitis from donors rendered microfilaria (MF) negative by seven consecutive monthly doses of milbemycin oxime (500 micrograms/kg) were transplanted into three previously uninfected and untreated dogs. Two dogs received reciprocal combinations of treated and untreated D. immitis and the third received untreated adults of both sexes. A fourth dog served as an infected, milbemycin treated, non-transplanted control. Eleven weeks after pairing treated female with untreated male worms, a low-level microfilaremia developed in the recipient. Two of the three treated female worms recovered from this dog were non-fertile, and the third contained a small number of elongate and coiled embryos but no mature intrauterine (stretched) microfilariae (MFF). The dog receiving treated male and untreated female worms became microfilaremic after two weeks. Microfilaremia peaked at 37,000/ml 16 weeks after transplantation and declined over the next 20 weeks to 7,200/ml. Untreated females paired with treated males either became non-fertile or exhibited low numbers of developing embryos and MFF scattered throughout their reproductive tracts. Pairing of untreated male and female worms produced a mcirofilaremia during the second post-operative week, which plateaued around 15,000 MFF per ml. Females recovered after this pairing contained a normal pattern of embryonic development, including stretched MFF. There were no significant differences in the percentage composition or absolute numbers of developing and mature sperm in the reproductive tracts of treated and untreated male worms. However, the resumption of MF production in one milbemycin treated female worm after pairing with normal males and failure of treated males to sustain MF production in untreated female worms suggest that milbemycin oxime impairs the sexual competence of male D. immitis. This may explain the ability of this drug to bring about long term suppression of microfilaremia without immediate adulticidal activity.

Animals↗
PubMed1993

Induction of protective immunity against larval Onchocerca volvulus in a mouse model.

BALB/cBYJ mice were immunized against larval Onchocerca volvulus by subcutaneous injection of normal, irradiated, or freeze-thaw-killed Onchocerca sp. larvae. The mice received challenge infections of O. volvulus third-stage larva (L3) contained in diffusion chambers implanted subcutaneously. At two-weeks postinfection, the diffusion chambers were removed and larval survival was assessed. When mice were immunized a single time with 35-krad-irradiated or normal O. volvulus L3, there was a significant reduction in the survival of challenge parasites. However, there was little or no reduction in challenge worm survival when mice were immunized a single time with freeze-thaw-killed O. volvulus L3 or fourth-stage larva (L4), or irradiated O. lienalis L3. When a second dose of freeze-thaw killed O. volvulus L3 or irradiated O. lienalis L3 was administered, there was a significant reduction in parasite survival in immunized mice. Immunization with O. volvulus L4 or a combination of L3 and L4 failed to confer protection. These results demonstrate that mice can be immunized against larval O. volvulus and that diffusion chambers are an efficient method for studying protective immunity to this parasite in a mouse model.

Animals↗
PubMed1992

Identification of surrogate rodent hosts for larval Onchocerca lienalis and induction of protective immunity in a model system.

The objectives of this project were to screen a variety of inbred rodent species and strains to determine their usefulness as surrogate hosts for the study of the early larval development of Onchocerca lienalis and then to use a selected model to study the induction of protective immunity. In the primary screen, 6 strains of mice, 5 strains of rats, jirds, and multimammate rats were tested. Animals were infected with fresh O. lienalis by subcutaneous implantation of third-stage larvae (L3) contained in diffusion chambers covered with 5.0-microns pore-size membranes. After 7 days the chambers were recovered, and larval viability and growth were assessed. Approximately one-half of inoculated larvae were recovered alive regardless of the host tested. Larvae were implanted in CBA/J and DBA/2J mice in chambers covered with membranes that prevented host cells from entering; survival and growth rates of the larvae were not altered by the absence of cells from the chambers. Cryopreserved larvae were implanted in chambers with 5.0-microns pore-size membranes in CBA/J and DBA/2J mice and Wistar Furth rats for 3-28 days. No statistically significant difference was seen in the larval recoveries on days 3-28 in all 3 hosts. Statistically significant increases in length were seen in the 3 strains from day 3 to day 14, after which growth appeared to cease. Molting from L3 to fourth-stage larvae was observed in all 3 hosts beginning on day 3, with most larvae completing the molt by day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Experimental ocular onchocerciasis: local and systemic antibody and cell-mediated immune responses.

Hartley guinea pigs injected subconjunctivally with Onchocerca lienalis (OL) microfilariae (Mf) develop punctate corneal opacities resembling the punctate keratitis of human onchocerciasis. Antibody production and antigen-induced proliferative responses were studied in conjunctival-associated lymphoid tissues (CALT), spleens (SL) and peripheral blood lymphocytes (PBL) from experimentally infected guinea pigs. Cultured single cell suspensions of CALT, SL and PBL were assayed for IgG1, IgG2, IgA and IgE antibody production. IgG1, IgG2, and IgA Onchocerca-specific antibodies were found in culture supernatants of CALT, SL and PBL. When initiated 10 days after a challenge injection of OL, CALT cultures produced antibody levels equal to or less than those produced by the corresponding SL cultures. When initiated 66 days after the last injection of Mf, CALT cultures produced significantly more antibody than the corresponding SL cultures. Blastogenic responses to OL Mf antigen were observed in peripheral and splenic lymphocytes of OL-infected guinea pigs. Animals given subconjunctival injections of Mf followed by treatment with a microfilaricide had greater responses to OL antigen than those given Mf alone, while responses to phytomitogens were similar in drug-treated and non-treated animals. The CALT was locally immunologically responsive against the subconjunctivally injected OL Mf, with the capacity for localized memory responses. The local immunologic responses to conjunctival Onchocerca microfilariae may play a significant role in the immunopathological reactions of ocular onchocerciasis.

Animals↗
PubMed1990

Synthetic and naturally occurring retinoids inhibit third- to fourth-stage larval development by Onchocerca lienalis in vitro.

A series of synthetic retinoids was screened for the ability to inhibit the third-to fourth-stage larval molt by Onchocerca lienalis in vitro. Of the 14 retinoids tested, eight gave significant inhibition of the molt at a concentration of 30.6 microM or less. Probit analysis of dose-response data collected for these active compounds indicated values for ED50 in the range of 3.7-17.1 microM. In general, the most active of these N-substituted retinamides were those with small alkyl or monohydroxy alkyl substituents. The most active of these was all-trans-N-(2-hydroxyethyl)retinamide with an ED50 of 3.7 microM. Both the all-trans and 13-cis isomers of the alkyl substituted derivatives were active, the all-trans-N-hydroxyethyl derivative being approximately 5 times as active as the corresponding 13-cis isomer. The N-2,3 dihydroxypropyl derivative, two derivatives with aromatic side chains and three N-(retinoyl)amino acids were inactive by the criteria set in the initial screening. There was no strict correlation between growth regulating activity against O. lienalis and binding affinity for a retinol binding protein from Onchocerca gibsoni.

Animals↗
PubMed1988

Abnormal patterns of embryogenesis in Dirofilaria immitis treated with ivermectin.

The percentage composition and spatial distribution of embryogenic stages in the uteri of female Dirofilaria immitis were examined at various times after treatment with a microfilaricidal dose of ivermectin and compared to nontreated parasites. Worms sampled 42 days post-treatment (PT) exhibited an increased proportion of stretched microfilariae in the distal portion of the uterus. A decreased proportion of developed embryos was noted in the mid body region of worms sampled 42 days PT, and these forms were completely absent from the proximal area of the uterus. Relative numbers and spatial distribution of other stages remained virtually identical to controls. Radical changes in the composition and spatial distribution of embryogenic forms were noted in the uteri of a single worm sampled 80 days PT. Unlike nontreated parasites and worms sampled 42 days PT, stretched microfilariae constituted the predominant form in the distal uterus of this worm, and these stages were found in decreasing numbers throughout the proximal segments. Also, the intermediate embryogenic stages were either rare or absent.

Animals↗
PubMed1988

Experimental ocular onchocerciasis in cynomolgus monkeys. II. Chorioretinitis elicited by intravitreal Onchocerca lienalis microfilariae.

Chorioretinitis due to onchocerciasis is a major cause of blindness, and the pathogenesis is poorly understood. We have developed an experimental model for onchocercal chorioretinitis using cynomolgus monkeys (Macaca fascicularis). Two normal monkeys and two monkeys which had received prior sensitization with subcutaneous injections of live Onchocerca lienalis microfilariae were given intravitreal injections of either 0, 10, 50 or 500 live microfilariae. Posterior segment changes included disc edema, venous engorgement, retinal vasculitis, intraretinal hemorrhage, and progressive retinal pigment epithelial (RPE) disturbances. Histopathological findings included perivascular infiltrates with eosinophils, eosinophilic choroiditis, and RPE hypertrophy, hyperplasia and loss of pigment. Microfilariae in the retina had no surrounding inflammation but were found adjacent to areas of RPE alterations. Overall the inflammatory reaction in the two unsensitized monkeys was more severe than that seen in the sensitized monkeys. The retinal appearance of the monkeys resembled that found in human onchocerciasis, and this model appears to be a promising one for future investigations.

Animals↗
PubMed1988

Occurrence of some blood and intestinal parasites in dogs in Curaçao, Netherlands Antilles.

In August 1986, 133 dogs at the Veterinary Service of the Netherlands Antilles and the SPCA of Curaçao were examined for microfilaremia and for evidence of gastrointestinal parasitism. Microfilariae of Dipetalonema reconditum were present in 27.8% of the dogs examined with no significant difference in the infection rate between domestic and feral dogs. Microfilariae of the canine heartworm Dirofilaria immitis were found in 9% of the dogs with a significantly higher rate of infection in domestic (pet) dogs (13.5%) than in feral dogs (3.4%). Of the intestinal parasites observed Ancylostoma sp. was present in the highest percentage of dogs (68.4%) followed by Toxocara sp. (7.5%). Other parasites were present in less than 5% of the dogs examined and included, in decreasing order of prevalence, Spirocerca sp., Giardia sp., coccidia, Taenia sp. and Trichuris sp. The present paper presents the first evidence of Di. reconditum on Curaçao and suggests the introduction of D. immitis to the island within the 10 years preceeding this report. The persistently high rate of infection with Ancylostoma underscores the continuing risk of cutaneous larva migrans to human beings in the region.

Animals↗
PubMed1988

Autoantibody induced by experimental Onchocerca infection. Effect of different routes of administration of microfilariae and of treatment with diethylcarbamazine citrate and ivermectin.

Hartley guinea pigs were injected with microfilariae (Mf) of Onchocerca lienalis as a model for acute inflammatory responses to Mf in human Onchocerca volvulus infection. IgG autoantibody reactive with a 3 M KCl extract of guinea pig cornea was detected by ELISA in the serum of guinea pigs injected with O. lienalis Mf three or more times sub-conjunctivally, or two or more times subcutaneously. Administration of the microfilaricides diethylcarbamazine citrate and ivermectin did not alter the proportion of animals expressing autoantibody or the mean autoantibody titer. The severity of acute corneal inflammatory reactions to Mf was similar in animals with and without circulating autoantibody. Although autoantibody responses did not correlate with acute corneal inflammatory reactions to dead Mf, the ability of Mf to induce formation of an antibody reactive with a component of autologous cornea suggests that autoimmune mechanisms might participate in chronic onchocercal lesions in the cornea, eg, sclerosing keratitis.

Animals↗
PubMed1988

Analysis of glutathione-enhanced differentiation by microfilariae of Onchocerca lienalis (Filarioidea: Onchocercidae) in vitro.

Reduced glutathione (GSH), but not its oxidized form (GSSG), stimulated development of Onchocerca lienalis microfilariae to the late first-larval stage in vitro. The degree and frequency of development was dose-related with a peak of activity at 15 mM, a concentration that is similar to known intracellular levels of GSH. To determine the mode(s) of action of this multifunctional compound, other reducing agents (L-cysteine, dithiothreitol), cysteine delivery agents (N-acetyl-L-cysteine, L-thiazolidine-4-carboxylic acid, L-2-oxothiazolidine-4-carboxylic acid), cysteine analogues (S-methyl-L-cysteine, D-glucose-L-cysteine, cysteine ethyl ester), free-component amino acids of GSH (glutamic acid, cysteine, and glycine), a specific metabolic inhibitor of gamma-glutamyl synthetase (buthionine sulfoximine), and an inhibitor of gamma-glutamyl transpeptidase (gamma-glutamyl glutamic acid) were also tested at concentrations of 0.01-50 mM in this system. N-acetyl-L-cysteine at 1-5 mM and D-glucose-L-cysteine at 2.5-10 mM significantly enhanced development. In contrast to those worms maintained in GSH-supplemented medium, microfilariae exposed to GSH for only the first 24 hr showed no enhancement by day 7 in culture. Neither buthionine sulfoximine nor gamma-glutamyl glutamic acid at 0.01-35 mM inhibited the effects of 15 mM GSH or 1 mM N-acetyl-L-cysteine. Results indicate that GSH or other cysteine analogues possessing a free sulfhydryl group must be present in the extranematodal environment to support microfilarial differentiation in vitro.

Animals↗
PubMed1987

Gastric gnathostomiasis in a cat.

A mass found in the stomach of a 10-year old cat contained a female worm of the genus Gnathostoma. The mass was described as a muscular pseudogranuloma induced by the worm. Although the worm species could not be ascertained, it was concluded that the cat served as an aberrant host for a Gnathostoma sp that usually infects wild mammals in the area.

Animals↗
PubMed1987

Effect of diethylcarbamazine citrate and anti-inflammatory drugs on experimental onchocercal punctate keratitis.

Subconjunctivally injected Onchocerca lienalis microfilariae (Mf) migrate into the guinea pig cornea, resulting, when the microfilariae die, in punctate stromal opacities resembling those of human onchocerciasis. Administration of diethylcarbamazine citrate (DEC-C) following subconjunctival injection of Mf increased the proportion of dead Mf in the cornea, the number of punctate opacities and the extent of peripheral corneal neovascularization. Betamethasone (a synthetic steroid) and lodoxamide tromethamine (an inhibitor of mediator release from mast cells) inhibited the formation of punctate opacities. Chlorpheniramine maleate and cimetidine (H1 and H2 histamine receptor antagonists), given together, did not alter the formation of punctate opacities but inhibited the peripheral corneal neovascularization. These observations suggest that mast cell mediators other than histamine may be of importance in the formation of the corneal punctate opacities.

Animals↗
PubMed1987

Studies of the growth-regulating effects of ivermectin on larval Onchocerca lienalis in vitro.

At concentrations of 0.1-100 ng/ml ivermectin inhibited L3-L4 molting by Onchocerca lienalis in vitro. The degree of inhibition was dose-dependent with a significant effect apparent at 0.1 ng/ml and complete inhibition occurring at 100 ng/ml. The ED50 for molt inhibition was 0.19 ng/ml. Molt-inhibiting levels of the drug were not acutely toxic to the worms. In the presence of 10 ng/ml, a concentration giving 95% molt inhibition, motility at day 7 postinoculation was 71% of that seen in nontreated controls. A more pronounced effect on motility was apparent in larvae under long-term cultivation in the presence of ivermectin. Kinetic studies indicated that the majority of the larvae respond irreversibly to the drug within the first 2 hr of exposure. Twenty-four hours of exposure were required for a maximal response. The inhibitory effects of ivermectin were less pronounced if larvae were allowed to develop under normal culture conditions for 24 or more hours prior to the initiation of drug treatment.

Animals↗
PubMed1986

Punctate keratitis induced by subconjunctivally injected microfilariae of Onchocerca lienalis.

An experimental model of human onchocercal keratitis was produced by injecting guinea pigs subconjunctivally with microfilariae (Mf) of Onchocerca lienalis. Actively motile O lienalis Mf spontaneously penetrated the central cornea and produced gray-white midstromal opacities, 0.2 to 0.4 mm in diameter, resembling those of human onchocercal punctate keratitis. Histologically, small foci of eosinophil and mononuclear cell infiltration associated with small pockets of interstitial edema were present in the central corneal stroma, with eosinophil infiltrates in the conjunctiva, episclera, limbus, and ciliary body. The severity of the punctate keratitis was increased by repeated subconjunctival inoculations of Mf. Punctate lesions were not seen following subconjunctival injection of Mf in animals previously hyperimmunized by three subcutaneous injections of Mf. Hyperimmunization may produce an immune response capable of destroying the subconjunctivally injected Mf and preventing their migration into the central cornea.

Animals↗
PubMed1986

Entomological studies at an enzootic Venezuelan equine encephalitis virus focus in Guatemala, 1977-1980.

The ecology of several potential mosquito vectors of Venezuelan equine encephalitis (VEE) alphavirus was studied in an enzootic focus of that virus on the Pacific coast of Guatemala over a four-year period. Four species-Culex taeniopus, Mansonia titillans, Culex nigripalpus and Aedes taeniorhynchus-were most prevalent during the wet season when transmission normally occurs. However, only Cx. taeniopus yielded VEE virus. The bloodfeeding patterns of these species revealed that Ae. taeniorhynchus and Ma. titillans fed almost exclusively on bovine and equine hosts. Conversely, Cx. nigripalpus was highly ornithophilic but occasionally fed on mammals. Cx. taeniopus exhibited a wide host range, utilizing both large and small mammals as well as birds and, rarely, reptiles. The versatility in feeding pattern displayed by this mosquito coupled with its ability to become infected with relatively low levels of enzootic VEE virus suggests that vertebrates other than rodents may serve as amplifying hosts in this habitat. Nepuyo virus was also isolated from Cx. taeniopus, suggesting that this mosquito might be an endemic vector of this rodent-associated bunyavirus. A single isolate of St. Louis encephalitis virus was made from Cx. nigripalpus.

Aedes↗