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Biomedical subjects

D I Grove

Publications and source records attributed to D I Grove.

At least 55 records · Page 3Linked to original sources
PubMed1986

Kinetics of cells in the intestinal mucosa of mice following oral infection with Ancylostoma ceylanicum.

A variety of cell types in the intestinal mucosa of mice has been observed following oral infection with Ancylostoma ceylanicum and the changes in their numbers quantified. The number of lamina propria mast cells increased following infection and reached a peak at 4 days; by 21 days the numbers had returned to normal levels. Globule leucocytes displayed a similar marked response but the numbers returned to within normal limits 7 days after infection. Granular intraepithelial lymphocytes did not alter significantly during the period of observation whereas non-granular intraepithelial lymphocytes declined in numbers following infection and were significantly decreased by 3 weeks. Goblets cells showed a similar response to infection as lamina propria mast cells and reached a peak level at 4 days. Following initial fluctuations in eosinophil numbers there was a substantial increase in the numbers of these cells with peak levels being reached at 21 days; eosinophil numbers then remained elevated for the duration of observation. Partial villous atrophy was seen 4 days after the arrival of larvae in the small intestine with maximum reduction in the length of villi at 7 days. Thereafter, there was a return to normal length followed by a significant elongation in villus length 28 days after infection. The influences of these various cell types on the expulsion of intestinal parasites are discussed.

Ancylostomiasis↗
PubMed1986

Strongyloides stercoralis infections in the muscles of mice: a model for investigating the systemic phase of strongyloidiasis.

The sequence of events following infection of mice with the intestinal nematode, Strongyloides stercoralis, has been observed. Most infective larvae passed to the muscles where they did not develop further. In mice given primary infections, larvae were found in muscles for the first 9 d or so, then disappeared spontaneously. This was associated with an inflammatory reaction, predominantly eosinophilic and histiocytic in nature, around dying larvae. In mice exposed to the worms previously, both inflammation and worm destruction were hastened indicating the acquisition of resistance. A number of immunological parameters were measured in both primary and challenge infections. Specific antibodies of the IgM and IgG classes appeared, a marked immediate hypersensitivity reaction to injected antigen developed, and a transient blood eosinophilia occurred. No effects on phytohemagglutinin-induced spleen cell transformation were discerned, nor was transformation induced by specific antigen. It is concluded that this system provides a potentially useful model for investigating the systemic phase of strongyloidiasis, particularly with respect to assessing anthelmintic efficacy and the functions of fractionated antigens.

Animals↗
PubMed1986

Experimental infection of humans with Ancylostoma ceylanicum: clinical, parasitological, haematological and immunological findings.

Experimental infection of two human volunteers with Ancylostoma ceylanicum produced patent infection. Following percutaneous infection with 1200 infective larvae, there was no evidence of skin eruption, however, severe abdominal discomfort was experienced by both subjects coincidently at various intervals. Eggs appeared in the faeces five weeks after infection; low level excretion continued until termination of the infection 30 weeks after inoculation. Infection had no significant effect on haemoglobin concentrations, total white cell counts, platelet levels or spontaneous and phytohaemagglutinin-induced lymphocyte transformations in either of the infected volunteers. Persistent eosinophilia began four weeks after infection in both infected persons; lymphocytes from one subject responded transiently to stimulation with larval antigen while lymphocytes from both infected subjects responded to stimulation with adult worm antigen. Specific IgM and IgG antibodies appeared two and six weeks after infection, respectively, and persisted for the duration of the experiment.

Ancylostomiasis↗
PubMed1985

Scanning electron microscopy of Ancylostoma ceylanicum and its site of attachment to the small intestinal mucosa of the dog.

The relationship between the hookworm Ancylostoma ceylanicum and the host intestinal mucosa in situ has been examined by using an in vivo fixation technique and scanning electron microscopy. Heads of the adult worms were buried deeply in the mucosa of the dog's small bowel. At some sites of attachment there was severe atrophy and ulceration of the immediately surrounding villi. Superficial deposits of fibrillar material with many enmeshed erythrocytes were associated with these attachment sites. When adult worms became removed after fixation, large numbers of erythrocytes could be seen at the base of the ulcers. Examination of the morphological details of adult A. ceylanicum revealed the characteristic mouthparts of large outer ventral teeth and smaller inner teeth. The distance between adjacent transverse cuticular striations was measured as 5.2 microns. The wide separation of the externolateral ray from the closely related mediolateral and posterolateral rays was illustrated together with the functi characteristic mouthparts of large outer ventral teeth and smaller inner teeth. The distance between adjacent transverse cuticular striations was measured as 5.2 microns. The wide separation of the externolateral ray from the closely related mediolateral and posterolateral rays was illustrated together with the functi characteristic mouthparts of large outer ventral teeth and smaller inner teeth. The distance between adjacent transverse cuticular striations was measured as 5.2 microns. The wide separation of the externolateral ray from the closely related mediolateral and posterolateral rays was illustrated together with the functional relationship of male and female copulating worms.

Ancylostoma↗
PubMed1985

Ancylostoma ceylanicum: immunization with soluble worm extract and responses to challenge infection of dogs.

When dogs were immunized with soluble extract of adult Ancylostoma ceylanicum antigen, they were partially resistant to challenge infection in this model of human hookworm infection. Two immunizing doses, each of 1 mg protein suspended in Freund's complete adjuvant, were administered to one group of animals 1 and 3 weeks prior to infection with 5000 larvae. When compared with control dogs given the same infective dose, fecal egg excretion and intestinal adult worm burden in the immunized animals were reduced by 59 and 74%, respectively. Infection had no significant effect on hemoglobin concentrations, mean red cell volumes, total white cell counts, platelet levels, or spontaneous and phytohemagglutinin-induced lymphocyte transformations in both control and immunized animals. Both groups developed an eosinophilia, and lymphocytes from the immunized dogs responded transiently to stimulation with both larval and adult worm antigens. Specific IgM antibodies were transitory in both groups of dogs following infection. IgG antibodies developed significantly 2 weeks after infection in the immunized group; however, they did not appear until 4 weeks after infection in the control group. Both groups developed IgA antibodies 1 week after infection. They were maintained in the control dogs, in contrast to the levels in immunized animals which subsided rapidly 4 weeks after infection. Therefore, when animals are injected with soluble adult worm antigen prior to infection, specific protective immunity is acquired.

Ancylostoma↗
PubMed1985

Resistance of dogs to reinfection with Ancylostoma ceylanicum following anthelmintic therapy.

A model of human hookworm infection has been developed which shows that dogs with chronic hookworm infection are considerably resistant to reinfection one month after the termination of the primary infection with anthelmintics. Challenge and control dogs were infected with 1,800 larvae and the infection was followed for six weeks. When compared with control dogs, faecal egg excretion and intestinal adult worm burdens in challenge dogs were reduced by 85% and 77%, respectively. Infection had no significant effect on haemoglobin concentrations, total white cell counts, platelet levels or spontaneous and phytohaemagglutinin-induced lymphocyte transformations in both control and previously infected dogs. Both groups of dogs developed an eosinophilia and lymphocytes responded transiently to stimulation with both larval and adult worm antigens, although there were no significant differences between the two groups of animals. Specific IgM antibodies were transient in both groups of animals following infection. Specific IgG antibodies were present at high levels before infection in challenge dogs when compared with control dogs, and fell transiently after challenge; three weeks after infection, IgG antibodies appeared in the control animals and titres continued to rise during the period of observation. Challenge dogs also developed specific IgA antibodies three weeks after infection, and these remained at high levels, but these antibodies were not detected in control dogs. Thus, dogs infected with this strain of the hookworm, Ancylostoma ceylanicum, which has been shown to infect man, develop functional protective immunity. These findings improve prospects for vaccine development.

Ancylostomiasis↗
PubMed1985

Interactions of Strongyloides ratti free-living and skin-penetrated infective larvae and parasitic adults with serum and cells in vitro.

When Strongyloides ratti free-living infective larvae were incubated with peritoneal exudate cells from normal or previously infected mice, cell attachment occurred only in the presence of normal (NMS) or immune mouse serum (IMS). This non-specific effect was transitory with larvae being alive and free of cells 24 h after incubation. Cell attachment was mediated by complement. When incubated with infective larvae which had penetrated mouse skin, both normal and immune cells attached to larvae in the absence of serum. This effect was again transitory except when immune cells or immune serum were present, indicating a specific immunological mechanism. Again, larvae remained viable. When incubated with isolated parasitic adult worms, persistent cell attachment occurred in the presence of immune serum, immune cells or both, but all worms remained viable. This system provides a means for investigating the mechanisms of resistance to reinfection in strongyloidiasis.

Adhesiveness↗
PubMed1984

The anticoagulant effects of the hookworm, ancylostoma ceylanicum: observations on human and dog blood in vitro and infected dogs in vivo.

Extracts of adult Ancylostoma ceylanicum prolonged the prothrombin time (PT) and partial thromboplastin time with kaolin ( PPTK ) of both human and dog plasmas in vitro. Excretory/secretory (E/S) products of these worms had similar effects while larval extract prolonged the PTTK only. Thus, the anticoagulant activities of this parasite are dependent upon the stage of the worm's life cycle. Collagen- and ADP-induced platelet aggregation were inhibited by adult and larval extracts. When the peripheral blood and bleeding times of dogs with varying worm burdens were examined, the only abnormality was shortening of the PTTK in the most heavily infected animals. Homogenates of dog small bowel subjacent to adult hookworms prolonged the PT of dog plasma and electron microscopical examination of this tissue revealed aggregation of platelets in blood venules without fibrin deposition. Thus, this study provides evidence that the anticoagulant properties of hookworms may have biological significance in infected animals.

Ancylostoma↗
PubMed1984

Purification of an anticoagulant from the body fluid of Ascaris suum.

An anticoagulant has been purified from the body fluid of Ascaris suum by sequential passage through Sephadex G-50, CM-cellulose and Sephadex G-25 columns then treated with 2 M NaCl, passaged through a Sephadex G-25 column, separated from the phosphate buffer by precipitation of the latter with the CaCl2, then passaged through a Sephadex G-10 column in water. In the body fluid of the worm, the anticoagulant is ionically-bound to a carrier substance. The complex can be split by treatment with 2 M NaCl. The molecular weight of the anticoagulant is slightly less than 1400.

Animals↗
PubMed1984

Transmission electron microscopical studies of the site of attachment of Ancylostoma ceylanicum to the small bowel mucosa of the dog.

The host-parasite interaction at the site of attachment of the adult hookworm, Ancylostoma ceylanicum, to the small bowel mucosa of the dog has been examined by transmission electron microscopy. The lamina propria around the heads of the worms showed intense infiltration with neutrophilic and eosinophilic leucocytes, and plasma cells were also prominent. Erythrocytes were extravasated within the lamina propria while the portions of mucosa engulfed into the buccal cavities of the worms were necrotic and included aggregates of collagen fibres. Within the lumina of the worms were erythrocytes in varying stages of lysis together with other necrotic debris. The mucous membrane adjacent to the heads of the worms was ulcerated while more distant enterocytes were small, distorted and displayed various degrees of microvillar loss. Many mucosal blood vessels had platelet aggregates within their lumina but no fibrin deposition was observed. Vessels were often seen in the bases of the ulcers and were prone to rupture. Erythrocytes and leucocytes were seen in the dog intestinal lumen in close proximity to the bodies of the worms.

Ancylostoma↗
PubMed1984

Parasitological, hematologic, and immunologic responses in acute and chronic infections of dogs with Ancylostoma ceylanicum: a model of human hookworm infection.

A model of human hookworm infection has been defined with a strain of Ancylostoma ceylanicum that is known to be infective for humans. In the first experiment, dogs were infected with between 150 and 12,150 filariform larvae and followed up for six weeks. A direct relation was found between the size of infecting dose, fecal egg excretion, intestinal adult worm burden, and worm distribution in the bowel. Dogs with heavy infection developed bloody diarrhea and iron-deficient anemia. In the second experiment, dogs infected with 2,000 larvae excreted ova until autopsy 36 weeks after infection. Normocytic anemia and blood eosinophilia coincided with maximal egg excretion. Transitory lymphocyte stimulation was seen with adult worm antigen. The specific IgM antibody response was transient, but IgG antibodies persisted indefinitely. Marked skin immediate hypersensitivity and Arthus (but no delayed) hypersensitivity reactions were seen to injected larval and adult antigens. Thus, dogs develop both hookworm disease and chronic infections similar to those seen in humans.

Acute Disease↗
PubMed1984

Kinetics of intestinal lamina propria mast cells, globule leucocytes, intraepithelial lymphocytes, goblet cells and eosinophils in murine strongyloidiasis.

The changes in numbers of 6 cell populations in the intestine of mice at various intervals after primary and challenge infections with Strongyloides ratti have been quantified. The number of lamina propria mast cells increased 8 days after primary infection and reached a peak at 12 days. After secondary infection, there was a transient fall in mast cell numbers followed by a slow increase. Globule leucocytes showed a similar trend early in the primary infection and had reached normal levels after 28 days. After challenge infection, there was an early and rapid increase in their numbers. Granular intraepithelial lymphocytes did not alter significantly during the first 14 days, but were significantly greater 28 days after primary infection; they did not vary significantly after challenge infection. However, numbers of non-granular intraepithelial lymphocytes increased 10 days after infection, were elevated prior to the secondary infection at 28 days, then declined in numbers nearly 2 weeks after challenge infection. Goblet cells increased significantly 12 days after primary infection then declined rapidly. After challenge infection, there was an accelerated increase in numbers. Eosinophil numbers increased 4 days after infection, reached a peak at 12 days and then declined. After challenge infection, there was an augmented and accelerated increase in eosinophil numbers followed by rapid decline. The role of the various cells types in host defences against worms or in containment of the inflammatory responses evoked by these parasites are discussed.

Animals↗
PubMed1984

Loss of surface coat by Strongyloides ratti infective larvae during skin penetration: evidence using larvae radiolabelled with 67gallium.

The optimal conditions for labelling infective larvae of Strongyloides ratti with 67gallium citrate were determined. Radiolabelled larvae were injected s.c. into normal and previously infected rats. The distribution of radioactivity in these animals was compared with that in rats infected subcutaneously with a similar dose of free 67Ga by using a gamma camera linked to a computer system. Whereas free 67Ga was distributed throughout the body and excreted via the hepatobiliary system, the bulk of radioactivity in rats injected with radiolabelled larvae remained at the injection sites. Direct microscopical examination of these sites, however, revealed only minimal numbers of worms. When rats were infected percutaneously with radiolabelled larvae, it was found that most radioactivity remained at the surface, despite penetration of worms. When infective larvae were exposed to CO2 in vitro and examined carefully by light microscopy, loss of an outer coat was observed. It was concluded that infective larvae lose an outer coat on skin penetration.

Animals↗
PubMed1984

Investigation of the haemolytic effects of Ancylostoma ceylanicum: observations on infected dogs in vivo and human and dog blood in vitro.

Investigations into the probable role of haemolysins in the causation of hookworm anaemia have been undertaken in living infected dogs. Secondly, the effects of living hookworms and various worm products on erythrocytes in vitro have been assessed. In dogs infected with varying numbers of A. ceylanicum, severe microcytic anaemia developed in the most heavily infected animals six weeks after infection. Erythrocytes from the latter animals showed significantly greater autohaemolysis in the presence of added glucose. When serum bilirubin and methaemalbumin, plasma haemoglobin, urinary urobilinogin and osmotic fragility of their red cells were measured, however, no evidence of haemolysis was detected. Erythrocytes from these animals appeared normal under scanning electron microscopy. In in vitro studies varying concentrations of adult worm extract had no effect on the haemolysis of either dog or human erythrocytes in the presence or absence of glucose nor on their mechanical fragility. There was no increase in 51Cr release from dog or human labelled red cells when incubated with either adult worm extract or excretory/secretory products of worms. Living adult worms caused an increase in 51Cr release from human but not dog labelled erythrocytes. Thus, the role of haemolysins in the genesis of hookworm anaemia is minimal.

Ancylostoma↗
PubMed1983

Light and electron microscopical studies of the location of Strongyloides ratti in the mouse intestine.

This study was designed to define the precise anatomical location of Strongyloides ratti in the intestinal mucosa of the mouse. Light microscopy showed adult worms in vacuoles in close relationship with the columnar epithelium. Serial sections indicated that the adults wound their way circuitously through the mucosa, usually close to the crypts. Portions of worms were sometimes seen in the intestinal lumen. Electron microscopy demonstrated that adult worms were situated between the epithelial cells. They were never observed to penetrate the basement lamina and enter the lamina propria. Enterocytes were in close proximity to the cephalic end of worms, suggesting that the head of the moving worm forced the cells apart. More posteriorly along the worm, a fluid-filled vacuole surrounded the nematode. The surrounding epithelial cells were compressed and distorted but there was never any evidence of syncytial cell formation. The external cortical layer of worms was seen in some vacuoles, suggesting that ecdysis may occur in tunnels in the epithelium. It appears that S. ratti may create epithelial tunnels through which it moves, moults and deposits eggs. Since S. ratti is a mucosal-dwelling parasite, it is susceptible to attack by cellular elements of the host's defences.

Animals↗
PubMed1983

Infections with a Malaysian dog strain of Ancylostoma ceylanicum in outbred, inbred and immunocompromised mice.

The course of infection with a Malaysian dog strain of Ancylostoma ceylanicum was investigated in 15 inbred strains of mice, in outbred and inbred mice immunosuppressed with prednisolone, and in immunodeficient hypothymic mice. Oral, percutaneous and subcutaneous routes of infection, in both sexes of mice, were assessed. In only one instance was a single small adult male worm found. Following oral infection, larvae migrated from the stomach to the large bowel and then a proportion of worms penetrated the perianal skin. This was followed by the appearance of larvae in the lungs. Living 3rd-stage larvae were seen in the anterior small intestine, perianal skin and lungs for the 6 weeks of the study, with peak recoveries being at 12 h, 8 days and 3 weeks, respectively. It is clear that systemic migration of larvae occurs after oral infection, and it is possible that recirculation may occur. Only a small percentage of larvae penetrated the abdominal skin after being administered percutaneously. In subcutaneous infections, a small proportion of larvae moved rapidly from the site of injection and were recovered from the lungs 2 h after infection. Most larvae, however, migrated from the injection site over the ensuing few days. Living 3rd-stage larvae were seen in the lungs and in the small intestine for the 4 weeks of observation. The strain of A. ceylanicum employed does not complete its development in mice. Nevertheless, this model offers significant potential for studying the immune responses, as well as investigating the means by which these parasites evade host defences.

Ancylostoma↗