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S L James

Publications and source records attributed to S L James.

At least 73 records · Page 4Linked to original sources
PubMed1989

Calcified cerebral sinus thrombosis in infancy--CT appearances with pathological correlation.

A case of calcified cerebral venous sinus thrombosis in an infant is described, with autopsy correlation. Calcification of sinus thrombosis is rare. A triangular calcific density was demonstrated in the superior sagittal sinus, with extension of linear calcification laterally into the transverse sinuses. Following intravenous contrast administration there was intense enhancement of the superior sagittal and transverse sinuses around the calcified thrombus. The cerebral hemispheres showed generalised atrophy. Autopsy confirmed a calcified venous sinus thrombus. Triangular calcium density within the sagittal sinus or linear calcification within the transverse sinuses would appear to be characteristic of calcified cerebral sinus thrombus.

Calcinosis↗
PubMed1989

Schistosome vaccines: current progress and future prospects.

Vaccination against human schistosomes in laboratory hosts is now a reality. A number of different parasite molecules have been shown to confer partial protective immunity against challenge infection with Schistosoma mansoni or Schistosoma japonicum in rodent or primate hosts. These antigens are unusually diverse in their structure and stage specificity. Interestingly, although all of the vaccine molecules characterized are situated in the tegument, their exposure on the parasite surface, in most instances, is transient and/or non-essential. The properties of four of these immunogens, glutathione-S-transferase (P26,28), paramyosin (Sm97), GP38, and GP18 are discussed. Despite the identification and recombinant synthesis of several promising protective antigens, vaccination of humans against schistosomiasis remains in the realm of fantasy. At the technical level, a major problem is the failure of any of the current vaccine immunogens and immunization protocols to induce levels of resistance sufficient for significant reduction of human infection or disease. Once this important hurdle is passed, human immunization trials should be attempted as the potential beneficial impact of a vaccine against schistosomiasis remains enormous.

Animals↗
PubMed1989

Acute regulation of the predominant organic solutes of the rabbit renal inner medulla.

High concentrations of organic solutes are present in the medulla of the antidiuretic kidney. However, their role in and response to acute changes in the diuretic state are unknown. In this study the organic solute content of the renal medulla was determined from extracts with the use of high-performance liquid chromatography following the acute dilution of the medullary interstitium during various forms of diuresis. After acute infusion of saline and furosemide, inner medullary urea, sodium, inositol, sorbitol, and betaine decrease significantly with no change in glycerophosphorylcholine (GPC) content. After diuresis, inner medullary urea and sodium contents eventually returned to control levels, although inositol, sorbitol, and betaine contents still remained low. Addition of antidiuretic hormone to the saline/furosemide infusion gave similar results. In contrast, induction of diuresis from mannitol infusion caused an acute decrease in all 4 organic solutes, whereas glucose infusion caused an acute decrease in all organic solutes except sorbitol. These data demonstrate that a decrease in all four organic solutes can accompany medullary dilution. However, GPC and sorbitol do not decrease when diuresis is induced by furosemide or glucose, respectively. In addition, the recovery of these compounds in a normally functioning kidney after diuresis is much slower than the regeneration of the sodium chloride and urea gradients.

Animals↗
PubMed1988

The influence of adjuvant on induction of protective immunity by a non-living vaccine against schistosomiasis.

Mice were protected against subsequent infection with Schistosoma mansoni by intradermal or s.c. vaccination with killed schistosomula or soluble parasite extracts and bacillus Calmette-Guérin (BCG). Treatment with i.p. immunization was somewhat less effective, whereas i.m. vaccination failed to elicit protective immunity. The level of resistance induced by intradermal immunization was influenced by the strain of BCG used, and isolated BCG cell walls did not reliably substitute for whole BCG organisms as adjuvant. Bordetella pertussis vaccine and saponin were also able to function as adjuvants for protective immunity in this model, whereas other immunopotentiators including Corynebacterium parvum and aluminum hydroxide were ineffective. No correlation between resistance to challenge infection and antibody levels was detected. Animals immunized intradermally using either protective or non-protective adjuvants all showed minimal humoral reactivity against schistosomulum surface Ag but strong IgG response to soluble parasite components including paramyosin, which is the major serologically recognized Ag in mice vaccinated intradermally with schistosome Ag plus BCG and is protective in this model. In contrast, a strong correlation was observed between resistance and Ag-specific cell-mediated reactivity, including IFN production by T lymphocytes in vitro and macrophage activation in vivo. These results further substantiate the hypothesis that protection in this model is based on cell-mediated immune effector mechanisms. Moreover, they may be of general relevance in the design of vaccination protocols using other Ag or against other infectious agents.

Adjuvants, Immunologic↗
PubMed1988

Induction of protective immunity against Schistosoma mansoni by vaccination with schistosome paramyosin (Sm97), a nonsurface parasite antigen.

Paramyosin (Sm97), a 97-kDa myofibrillar protein identified by the unusually monospecific antibody response induced by intradermal vaccination of mice with a complex soluble worm antigen preparation (SWAP) of adult Schistosoma mansoni administered with bacillus Calmette-Guérin (BCG), was purified and tested for its capacity to protect mice against challenge infection. When administered intradermally with BCG at total doses of only 4-40 micrograms per mouse, both the native molecule and a recombinant expression product containing approximately 50% of the whole protein were found to confer significant resistance (26-33%) against challenge infection, while 2 mg of unfractionated SWAP was required to induce similar levels of protection. In addition, paramyosin was shown to stimulate T lymphocytes from vaccinated mice to produce lymphokines [e.g., gamma interferon (IFN-gamma)] that activate macrophages to kill schistosomula. Neither schistosome myosin nor a heterologous paramyosin from a different invertebrate genus were protective, indicating a requirement for specific epitopes in the immunization. That the protection induced by paramyosin involves a T-cell-mediated mechanism was supported by the failure of anti-paramyosin antibodies to passively transfer significant resistance to infection to recipient mice. Lymphocytes from mice vaccinated with paramyosin were found to produce IFN-gamma in response to living schistosomula, suggesting that during challenge infection of vaccinated hosts, paramyosin (a nonsurface antigen) may elicit a protective T-cell response as a consequence of its release from migrating parasite larvae. Paramyosin-depleted SWAP was also found to be protective as well as stimulatory for T lymphocytes from SWAP-vaccinated mice, indicating that other antigens in this preparation may have immunoprophylactic potential. In summary, these results (i) suggest that the induction of T-cell-dependent cell-mediated immunity against soluble nonsurface antigens may be an effective strategy for immunization against multicellular parasites and (ii) in the case of schistosomes, identify paramyosin as a candidate vaccine immunogen in this category.

Animals↗
PubMed1988

Induction of protective immunity against Schistosoma mansoni by a non-living vaccine. VI. Antigen recognition by non-responder mouse strains.

Previous studies have shown that many strains of mice develop partial resistance to Schistosoma mansoni as a result of intradermal vaccination with soluble schistosome antigens plus BCG. However, P and BALB/c mice are non-responsive to this intradermal vaccination protocol. In this study, humoral and cellular responses to schistosome antigens in vaccinated P and BALB/c mice were compared to those in protected C57BL/6 mice to identify an immune correlate to resistance in this model. Levels of circulating IgG and IgM antibodies to soluble adult worm antigens, as measured by ELISA, were comparable between strains. Moreover, Western blot analysis revealed no qualitative differences in antibody reactivity, with sera from vaccinated animals of all three strains recognizing the antigen previously identified as Sm-97 (paramyosin). However, vaccinated P and BALB/c mice showed specific defects in cell-mediated immunity to schistosome antigens, including decreased production of macrophage-activating lymphokines and an inability to produce activated macrophage effector cells in vivo at the site of antigen challenge. These observations strengthen our hypothesis that the intradermal vaccine acts through induction of T-cell-mediated immune resistance mechanisms.

Animals↗
PubMed1988

Genetic complementation of defects in vaccine-induced immunity against Schistosoma mansoni in P- and A-strain inbred mice.

Inbred P- and A-strain mice are deficient in their capacity to develop resistance to challenge infection in response to vaccination with irradiated cercariae of Schistosoma mansoni and are also defective in their cell-mediated response as assessed by the activity of antigen-elicited macrophages in killing schistosome larvae in vitro. In contrast, vaccinated (P x A)F1 mice displayed high levels of both immunity to challenge and macrophage larvicidal activity, indicating that the P- and A-strain defects in the vaccine-induced response are controlled by distinct genetic loci.

Animals↗
PubMed1988

Proximal tibial osteotomy in patients who are fifty years old or less. A long-term follow-up study.

Proximal tibial valgus osteotomy was performed for unicompartmental osteoarthritis in forty-five patients (fifty-one knees). The average age of the patients was forty-one years (range, twenty-three to fifty years), and the average length of follow-up was ten years. At follow-up, 70 per cent (thirty-six knees) were rated as good or excellent and 30 per cent (fifteen knees) were rated as fair or poor. There was no clear correlation between the quality of the result and the radiographic evidence of the severity of the arthritis preoperatively, the age of the patient at osteotomy, or the length of follow-up. There was a correlation between an improved result and an increased angle of correction after osteotomy, but the values were not statistically significant. The most important factor influencing the quality of results was the over-all level of disease in the knee as reflected in the preoperative knee score. Deficiency of the anterior cruciate ligament at the time of the osteotomy did not prevent a good result. We believe that proximal tibial osteotomy for unicompartmental arthritis of the knee is a good and effective procedure for patients who are less than fifty years old and who have an active life-style, and that lasting results can be achieved if the procedure is done early in the course of the disease.

Adult↗
PubMed1987

Schistosoma spp.: progress toward a defined vaccine.

During the last 2 decades, much was learned concerning the nature of acquired immunity in schistosomiasis, under experimental as well as field conditions. The knowledge is being applied now to design of a defined vaccine against this major parasitic disease. Several Schistosoma spp. antigens have been purified and shown to potentially protect in vivo. Determination of a method for presenting these antigens that will induce an optimal combination of cellular and humoral immune responses remains a critical step in vaccine development.

Animals↗
PubMed1987

Induction of protective immunity against Schistosoma mansoni by a non-living vaccine. V. Effects of varying the immunization and infection schedule and site.

Intradermal (i.d.) injection with non-living schistosome antigens plus bacterial adjuvant protects mice against subsequent infection with Schistosoma mansoni. This protection became apparent within 2 weeks after a single inoculation and persisted for at least 8 weeks. Administration of one or more booster immunizations enhanced the level of protection but never produced complete resistance to cercarial challenge under the conditions tested. All immunized mice recognized the Sm 97 antigen in adult worms, as measured by antibody reactivity in ELISA, although the level of reactivity did not correlate with the level of resistance. Significant protection was observed when mice were immunized in the skin of the chest, the footpad or at the base of the tail if challenge infection was administered percutaneously either on the abdomen or back. However, when mice were infected by cercarial exposure of the tail skin, the level of resistance was consistently lower regardless of the immunization site. Vaccinated mice were not resistant to infection with lung stage parasites. These results demonstrate that the i.d. vaccine induces significant and persistent resistance in mice, the level of which is strengthened by booster immunization. The resistance is unrelated to inflammation at the site of immunization. However, immune response at the challenge site may play a critical role in the effector mechanism of resistance in this model.

Animals↗
PubMed1987

Effects of inhibitors of tumoricidal activity upon schistosomulum killing by activated macrophages.

Larvae of the helminth parasite Schistosoma mansoni are efficiently killed in vitro by lymphokine-activated macrophages, leading to the hypothesis that these cells may participate in the effector mechanism of protective immunity against schistosomiasis. Larvacidal activity has also been demonstrated in the IC-21 macrophage cell line in the absence of a demonstrable respiratory burst, indicating that macrophages possess nonoxidative mechanisms of schistosomulum killing. In this study, we demonstrated that IC-21 larval killing was most effective when contact was allowed between cells and target. Nonoxidative larvacidal activity was prevented by protein synthesis inhibitors, by the inhibition of microtubule polymerization, and by tosyllysylchloromethylketone but not by other inhibitors or substrates of tryptic or chymotryptic protease activity. The addition of excess iron to the culture also prevented IC-21-mediated larval killing, suggesting that the production of an iron-binding molecule may be involved. In contrast, the addition of excess thymidine or arginine did not reverse macrophage larvacidal activity, nor did lysosomotropic agents that depress the activity of acid hydrolases. Under appropriate conditions of activation and surface membrane stimulation, IC-21 cells could be induced to release soluble cytotoxic factors retaining larvacidal activity. These observations provide insight into the mechanism of macrophage-mediated schistosome killing, in comparison to the cytotoxic mechanisms described in the better-studied tumoricidal models, and supply a basis for further biochemical investigation of macrophage function against a multicellular target.

Animals↗
PubMed1987

Macrophage activation as an immune correlate to protective immunity against schistosomiasis in mice immunized with an irradiated, cryopreserved live vaccine.

Immune responses against Schistosoma mansoni were evaluated in C57BL/6 mice injected with one of two populations of irradiated schistosomules, the larval preparations differing only in the degree of freezing-induced damage sustained upon cryopreservation. Mice injected with larvae which successfully withstood cryopreservation showed a significant reduction in worm burden following cercarial challenge. No protection was achieved in mice which received larvae damaged by a suboptimal thawing rate. Parallel comparison of several humoral and cellular responses in mice which received either inoculum revealed that induction of activated macrophages and production of macrophage-activating lymphokine activity were the strongest correlates to development of protective immunity. Protected mice also showed marginal 30-min skin test reactivity and weak but transient 24-h delayed-type hypersensitivity to a soluble adult worm preparation. In contrast, indistinguishable levels of circulating antibodies to soluble and tegumental antigens developed in the two immunization groups, and antigen-stimulated lymphocyte blastogenic responses were strong and essentially equivalent in magnitude. These studies strongly suggested that in this new model for investigating anti-schistosome effector mechanisms, responses contributing to the development of activated macrophages may be essential for induction of protective immunity.

Animals↗
PubMed1987

Genetic association of defects in macrophage larvicidal activity and vaccine-induced resistance to Schistosoma mansoni in P strain mice.

In contrast to most inbred strains, P mice fail to develop significant resistance to Schistosoma mansoni infection as a result of vaccination with irradiated cercariae. Vaccinated P mice also exhibit a defect in macrophage activation for killing of larval schistosomes upon specific-antigen challenge in vivo. To examine the genetic basis of these defects in vaccine-induced immunity, inheritance of the two traits was examined in (C57BL/6 X P)F1, F2, and reciprocal backcross generations. The defect in macrophage function which characterizes the P strain parent was found to be inherited in a fully recessive manner and to be controlled by only one or two major genetic loci. Moreover, a highly significant correlation (P less than 0.0025) was observed between the level of macrophage larvicidal activity and the level of resistance to challenge infection in segregating generations. Such an association is consistent with a cause-and-effect relationship, providing strong in vivo evidence implicating activated macrophages as immune effector cells of resistance to S. mansoni in the mouse-irradiated-vaccine model.

Animals↗
PubMed1987

Prospects for a nonliving vaccine against schistosomiasis based on cell-mediated immune resistance mechanisms.

We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.

Adjuvants, Immunologic↗
PubMed1987

Vaccine-induced immunity in mice against Schistosoma mansoni trickle cercarial infections.

Experiments were performed to determine the level of protection in immunized mice to multiple small (trickle) Schistosoma mansoni cercarial challenges. C57BL/6 mice were immunized with either 50 Krad-irradiated cercariae or a soluble worm antigenic extract injected intradermally in conjunction with the adjuvant BCG. A series of cercarial challenges (40 cercariae per exposure), beginning approximately one month after immunization, was given at 4-week intervals. To prevent any contribution of egg-related pathology, the mice were exposed to male cercariae only. The results showed that highly significant levels of protection developed at all times after cercarial challenge. Regardless of the type of immunization or the number of cercarial challenges, the levels of protection which appeared after one, two, three, or four challenge exposures were nearly identical, and equalled those in mice exposed at a single time to a cumulative total of the several exposures. As expected, titers of anti-schistosome antibodies were higher in the immunized and challenged groups than in those challenged alone, and titers increased anamnestically after challenge infection. However, increased antibody titers were not associated with increased resistance in trickle challenged mice. Overall, we showed that the level of vaccine-induced immunity does not change, under these conditions, in the face of repeated cercarial challenges. Also, these results show that single mass cercarial challenges may legitimately be used in experimental situations to assess the effectiveness of vaccines which might be used in subjects repeatedly exposed to cercariae in field situations.

Animals↗