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S L James

Publications and source records attributed to S L James.

At least 109 records · Page 6Linked to original sources
PubMed1984

Macrophages as effector cells of protective immunity in murine schistosomiasis: macrophage activation in mice vaccinated with radiation-attenuated cercariae.

Cell-mediated immune responses contributing to macrophage activation were compared in mice that demonstrated partial resistance to challenge Schistosoma mansoni infection as a result of vaccination with radiation-attenuated cercariae or of ongoing low-grade primary infection. Vaccinated mice developed significant delayed hypersensitivity reactions to soluble schistosome antigens in vivo. Splenocytes from vaccinated animals responded to in vitro culture with various specific antigens (soluble adult worm extract, living or disrupted schistosomula) by proliferation and production of macrophage-activating lymphokines as did lymphocytes from S. mansoni-infected animals. Macrophage-activating factors produced by spleen cells from vaccinated mice upon specific antigen stimulation eluted as a single peak on Sephadex G-100 with a molecular weight of approximately 50,000 and contained gamma interferon activity. Moreover, peritoneal macrophages with larvicidal and tumoricidal activity were recovered from vaccinated mice after intraperitoneal challenge with soluble schistosome antigens, a procedure also observed to elicit activated macrophages in S. mansoni-infected animals. These observations demonstrate that vaccination with irradiated cercariae stimulates many of the same cellular responses observed after primary S. mansoni infection, and suggest that lymphokine-activated macrophages may participate in the effector mechanism of vaccine-induced and concomitant immunity to challenge schistosome infection. This is the first demonstration of a potential immune effector mechanism in the irradiated vaccine model.

Animals↗
PubMed1984

Cation induced changes in the rheological properties of purified mucus glycoprotein gels.

The effects of mono-, di- and trivalent ions on the rheological properties of a purified mucus glycoprotein gel have been investigated. Monovalent ions increased the fluidity of the gels in a concentration dependent manner. The effect of calcium was pH dependent; at neutral pH values this ion produced a maximum in the gel viscoelasticity at a concentration of 0.5 mM, whilst at pH 5.0 the increase in viscoelasticity was sustained up to 3.0 mM. The same concentrations of copper (II) at pH 5.0 had a similar but greater effect on the viscoelasticity. Al3+ at pH 3.0 increased the viscoelastic moduli throughout the range studied (0.1-2.0 mM), whereas iron made the gels more fluid at low concentrations, but increased the viscoelasticity to above control values at a concentration of 2.0 mM.

Animals↗
PubMed1984

Selected methods for the evaluation of the effects of drugs on mucus viscoelasticity and mucociliary clearance.

In order to rationally test the efficacy of mucolytic and mucospissic compounds, their effects upon mucus viscoelasticity, ciliary beat frequency (c.b.f.) and total mucociliary transport rate (t.t.r.) must all be determined. Methods are described which allow the measurement of the viscoelastic modulii of small (10 microL) quantities of mucus, while c.b.f. and t.t.r. are determined using the frog palate model.

Animals↗
PubMed1984

Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection.

Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.

Animals↗
PubMed1984

Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. II. Analysis of cellular responses.

Cellular immune responses against larval and adult schistosome antigens were studied in attenuated cercariae-vaccinated P and C57BL/6 mice to define differences correlating with the inability of P mice to develop vaccine-induced resistance to challenge Schistosoma mansoni infection. Vaccinated P mice failed to demonstrate delayed hypersensitivity upon skin-testing with soluble worm antigens, whereas mice of the highly resistant strain C57BL/6 developed a significant 24-hr response to worm antigens in vivo. Also, when schistosome antigens were injected i.p., vaccinated P mice failed to exhibit an activated macrophage response in vivo, whereas vaccinated C57BL/6 mice developed macrophages with significant larvicidal and tumoricidal activity at the site of specific antigen challenge. Immune sera from either vaccinated C57BL/6 or P mice were equally effective at opsonizing the schistosomula targets in the larvicidal assay. In vitro analyses of cellular defects revealed that although T lymphocytes from vaccinated P mice showed blastogenic responses to schistosome antigens that were similar in magnitude and kinetics to those of cells from the C57BL/6 animals, T cells from C57BL/6 mice produced higher levels of macrophage-activating lymphokines (LK), including gamma-interferon. Macrophages from control C57BL/6 mice were also more responsive to activation by LK than macrophages from P mice were, as assessed by stimulation of these cells to kill skin-stage schistosomula in vitro. These two aspects of cellular dysfunction in P mice had the combined effect of rendering P macrophages incapable of activation by LK from mice of their own strain, whereas macrophages from C57BL/6 mice were strongly activated by LK from vaccinated C57BL/6 mice in the same assays. Thus, a correlation exists between T lymphocyte/macrophage dysfunction and lack of resistance to challenge infection in vaccinated P mice, which suggests that delayed hypersensitivity response plays a major role in the immunity to S. mansoni infection that is induced by exposure to radiation-attenuated cercariae.

Animals↗
PubMed1984

Patellofemoral disorders: physical and radiographic evaluation. Part I: Physical examination.

Patellofemoral disorders present a diagnostic and therapeutic challenge to the orthopedic surgeon. By the sequential application of such basic diagnostic tools as inspection, palpation, and various measurements to a patient in standing, sitting, supine, and prone positions, a reproducible, comprehensive physical examination of the patellofemoral joint and entire lower extremity may be achieved.

Femur↗
PubMed1984

Patellofemoral disorders: physical and radiographic evaluation. Part II: Radiographic examination.

Evaluation of the patient with patellofemoral complaints requires a comprehensive physical and radiologic investigation. The tangential view is most helpful in the evaluation of such patellofemoral disorders as chondromalacia, lateral patellar compression syndrome, and recurrent subluxation or dislocation. Commonly utilized tangential views include those described by Hughston, Merchant, Laurin, and Ficat. Multiple calculations available for quantitation of abnormal tangential views include the sulcus angle, congruence angle, lateral patellofemoral angle, patella index, and patellofemoral index. Lateral radiographic views commonly utilized to evaluate the patellofemoral joint for patella alta or infera include those described by Blumensaat, Labelle and Laurin, and Insall and Salvati. Utilization of all of the available patellofemoral radiographic views and calculations is impractical and unnecessary. However, to ensure diagnostic accuracy, a routine consisting of a reproducible radiographic technique and various, easily performed calculations that aid in diagnosis must be adopted.

Femur↗
PubMed1984

Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. I. Analysis of antibody responses.

Inbred P4 strain mice have previously been shown to be uniquely defective in their resistance to challenge infection induced by irradiated cercariae of Schistosoma mansoni. To assess whether the low levels of resistance developed by vaccinated P mice could be due to a defective antibody response, we compared the anti-schistosomulum antibody responses in vaccinated P animals with those occurring in vaccinated C57BL/6J (B6) mice, a strain that consistently develops high levels of resistance to challenge infection. Our results indicate that vaccinated P mice develop levels of total anti-schistosomulum antibodies that are significantly lower than those occurring in B6 mice for at least 15 wk after immunization, with the exception of the fifth week, at which time the responses are indistinguishable. Further analysis revealed that the defect in P strain antibody response occurs specifically in the IgM isotype and that specific IgM levels in P mice are less than one-half the levels in B6 mice at every time point examined. In contrast, no differences in total IgM immunoglobulins were evident when sera from normal (nonvaccinated) P and B6 mice were compared. P mouse anti-schistosomulum IgG antibody responses reached the same levels as those observed in B6 mice by 5 wk after vaccination. However, a much faster decay in IgG antibody levels occurred after this time point in P animals. No differences were observed when the levels of anti-schistosomulum antibodies occurring in each of the major IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) were compared in sera from P and B6 mice vaccinated 4 wk previously. Similarly, vaccinated P and B6 mice were found to mount indistinguishable IgG anamnestic responses after challenge infection. Finally, no differences between vaccinated P and B6 mice were observed when immediate (30 min) skin test and mast cell degranulation responses to a soluble schistosome antigenic preparation were compared. The above findings suggest that P strain mice have a specific defect in their ability to mount IgM antibody responses after immunization with irradiated cercariae. The possible contribution of this defect in IgM response to the decreased resistance of vaccinated P mice to challenge infection is discussed.

Animals↗
PubMed1983

Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension.

Persistent pulmonary hypertension of the newborn is a syndrome consisting of severe hypoxemia and pulmonary hypertension that appears within hours of birth. Since certain leukotrienes (C4, D4, and E4) are known to produce some of the features of persistent pulmonary hypertension of the newborn, including pulmonary vasoconstriction, bronchoconstriction, decreased lung compliance, and pulmonary edema, we studied five newborns with the syndrome to determine whether these leukotrienes were present in their airways. We found leukotriene C4 and leukotriene D4 in the lung lavage fluids of all five newborns who had the clinical diagnosis of persistent pulmonary hypertension and who required ventilatory assistance. In contrast, leukotrienes were not demonstrated in a control group of 14 infants requiring ventilatory assistance who did not have the clinical diagnosis of persistent pulmonary hypertension. We conclude that leukotrienes may have a role in persistent pulmonary hypertension of the newborn.

Animals↗
PubMed1983

Surprising consequences of the tendency of pepsin to catalyze condensation reactions between small peptides.

Pepsin catalyzes numerous acyl-transfer reactions. Are peptic acyl-enzyme intermediates involved in such reactions? To start, we examine the cleavage of Leu-Trp-Met-Arg at pH 3.4-4.5 in the presence of 25 mM tryptophanamide. Substantial amounts of Leu-TrpNH2 are generated. However, the appearance of this acyl-transfer product cannot be attributed to the intervention of Leu-pepsin and its trapping by tryptophanamide. Experiment proves that Leu-Trp-Met-Arg affords Leu3, which, in turn, reacts with tryptophanamide to produce Leu-TrpNH2. Both the formation of Leu3 from Leu-Trp-Met-Arg and the conversion of Leu3 + tryptophanamide into Leu-TrpNH2 can potentially implicate the generation and trapping of a Leu-pepsin intermediate. Does experiment support either possibility? The answer is no. Our data show that most of the Leu3 derived from Leu-Trp-Met-Arg stems from an autocatalytic condensation process whereby Leu3 already present speeds the conversion of the leucine residues of unreacted Leu-Trp-Met-Arg into more Leu3. Technical problems have prevented us from determining whether the first Leu3 formed results from the trapping of an acyl-enzyme intermediate. The generation of Leu-TrpNH2 from Leu3 was studied primarily via a more tractable analogous reaction: Leu-Trp-Leu + tryptophanamide leads to Leu-TrpNH2. The mechanism governing these transformations is highly complex. Its major feature is an initial condensation between two molecules of substrate. All the examples investigated further illustrate the marked tendency of pepsin to catalyze condensation reactions between suitably constructed small peptides. The prevalence of these reactions complicates the interpretation of much data bearing on pepsin's mechanism of action.

Amino Acid Sequence↗
PubMed1983

An assessment of subject variability, subject-shoe interaction, and the evaluation of running shoes using ground reaction force data.

Several aspects of dynamic foot function were investigated using ground reaction forces obtained from five runners performing in five different shoes. A minimum of eight trials were necessary in order to obtain stable subject-condition values. Statistically significant subject-shoe interactions occurred for all parameters. It was therefore concluded that a knowledge of shoe characteristics independent of subject characteristics provided little useful information regarding the effects of the shoes tested on selected foot mechanics of the runners. The various subject-conditions were evaluated in an attempt to determine which was the best shoe. Selected descriptive data are presented and the 'best' shoe concept discussed.

Biomechanical Phenomena↗
PubMed1983

Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae III. Identification of a mouse strain, P/N, that fails to respond to vaccination.

Eleven strains of inbred mice were examined for their ability to develop resistance to challenge Schistosoma mansoni infection as a result of previous exposure to homologous cercariae that had been attenuated by high-dose irradiation. Two strains, C57B1/6J and BALB/c, demonstrated consistently high levels of vaccine-induced immunity (means of 64% and 58% resistance, respectively, when compared to control groups of the same strain) and were designated as 'high responder' strains to vaccination. Six other strains fell into an intermediate category, demonstrating moderate, yet statistically significant, levels of immunity resulting from vaccination (means of 30-50% resistance). Only one of the strains examined consistently failed to respond to vaccination by the development of significant levels of immunity to challenge infection. Animals of the P/N strain demonstrated a mean of only 15% resistance to challenge in five experiments and have been classified as 'low responders' to vaccination. P/N mice have previously been characterized as deficient in their ability to mount delayed hypersensitivity reactions, produce lymphokine and display macrophage activation for cytolysis of extracellular and intracellular targets in other experimental systems, suggesting that these immune responses may be critical to the establishment of vaccine-induced resistance to S. mansoni infection. The availability of high and low responder mouse strains should facilitate a genetic approach to characterization of the immune effector mechanism(s) of vaccine-induced resistance to S. mansoni infection.

Animals↗
PubMed1983

Activation of macrophages for microbicidal and tumoricidal effector functions by soluble factors from EL-4, a continuous T cell line.

Macrophages treated with culture fluids from EL-4 cells, a continuous T cell line, were activated to kill mKSA-TU-5 fibrosarcoma cells, amastigotes of Leishmania tropica, and schistosomula of Schistosoma mansoni. Active EL-4 factors eluted from Sephadex G-100 in two distinct regions: molecular weight 45,000 (activities induced killing of unrelated intracellular and extracellular targets) and molecular weight 23,000 (activities induced killing of extracellular targets only). These results confirm heterogeneity among activation signals for the induction of macrophage microbicidal and tumoricidal activities. Factors that induced cytocidal activity against extracellular tumor cells and schistosomula were distinct from those that induced destruction of intracellular amastigotes.

Animals↗
PubMed1983

Identification of surface antigens of schistosomula of Schistosoma mansoni recognized by antibodies from mice immunized by chronic infection and by exposure to highly irradiated cercariae.

Surface components of mechanically transformed schistosomula of Schistosoma mansoni were labeled by lactoperoxidase-catalyzed iodination. After solubilization with Triton X-100, antigens were identified by immunoprecipitation. Serum from chronically infected Swiss mice reproducibly precipitated seven major polypeptides with approximate molecular weights (X 10(3] of 94, 68, 45, 40 to 32, 22, and 16. The antigens of molecular weights (X 10(3] of 94, 40 to 32, 22, and 16 were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. Sera from several strains of infected inbred mice precipitated the same polypeptides. The antibodies produced during chronic infection were found to be stimulated by adult worms since sera from 6-week-infected animals precipitated none of the surface antigens, and the pattern produced by precipitation with antibodies from a mouse infected with male worms only was indistinguishable from the pattern obtained with sera from mice with bisexual infections. Antibodies from mice immunized with highly irradiated cercariae reproducibly precipitated major polypeptides of approximately (X 10(3] 94, 68, 45, 32, 22, 19, and 15 daltons. The antigens of (X 10(3] 94, 43, 32, 22, and 15 daltons were shown to be exposed on the parasite surface by interaction of the antibodies with intact labeled schistosomula. The 15 X 10(3)-dalton surface protein was recognized by sera from vaccinated, but not chronically infected, mice, suggesting that it represents a stage-specific immunogen present on schistosomula but not on adult worms. Sera from two inbred strains of mice which develop different degrees of immunity recognized the same antigens.

Animals↗
PubMed1983

Macrophages as effector cells of protective immunity in murine schistosomiasis. VI. T cell-dependent, lymphokine-mediated, activation of macrophages in response to Schistosoma mansoni antigens.

Macrophages from Schistosoma mansoni-infected mice kill significant numbers of skin stage schistosomula and murine fibrosarcoma cells in vitro. In order to determine whether the macrophage tumoricidal and larvicidal activation observed in mice as a result of S. mansoni infection are mediated through T cell-dependent (lymphokine) or B cell-dependent (antibody or immune complex) mechanisms, the development of macrophage populations with cytotoxic activity against schistosome larvae or tumor cells was monitored in S. mansoni-infected nude or mu-suppressed mice. Whereas peritoneal cells from S. mansoni-infected congenitally athymic mice had no activity in either assay, cells from mu-suppressed S. mansoni-infected mice showed cytotoxic activity equivalent to that of cells from untreated S. mansoni-infected counterparts. Cells from mu-suppressed uninfected mice were not activated. The mu-suppressed animals had no detectable nonspecific IgM or specific antischistosome IgM, IgG, or IgE antibodies and showed a 90% reduction in numbers of splenic IgM+ cells upon fluorescence activated cell sorter analysis. These results indicate that antibody is not required for in vivo activation of macrophages during S. mansoni infection. Further experiments showed that lymphoid cells from S. mansoni infected mice respond in culture with various specific antigens (such as living or dead whole schistosomula or soluble adult worm antigens) by production of factors capable of activating macrophages from uninfected control mice to kill schistosomula or tumor cells in vitro. Macrophage-activating factors were produced by T cell-enriched, but not T cell-depleted or B cell-enriched, populations from spleens of schistosome-infected mice in response to schistosome antigen. Similar lymphokines may be responsible for the macrophage activation observed during chronic murine schistosomiasis. These observations emphasize the potential contribution of T cell-mediated immune mechanisms in resistance to S. mansoni infection.

Animals↗
PubMed1983

Macrophages as effector cells of protective immunity in murine schistosomiasis. V. Variation in macrophage schistosomulacidal and tumoricidal activities among mouse strains and correlation with resistance to reinfection.

Mice of several inbred strains previously characterized as defective in various aspects of macrophage activation for tumor cell killing were utilized to compare the genetic control of induction of macrophage tumoricidal and schistosomulacidal activity and to examine the role of activated macrophages in concomitant immunity to Schistosoma mansoni infection. In all mouse strains tested, macrophage larvicidal activity developed concurrently with tumoricidal activity after in vivo bacillus Calmette Guérin or Corynebacterium parvum treatment. Lpsd strains, A/J, and P/N mice failed to develop macrophages capable of killing either tumor cells or helminth larvae in vitro, whereas C57BL/6J, C3H/HeN, and BALB/c mice all demonstrated strongly cytotoxic cells. In fact, analysis of the reactivity of peritoneal cells from C. parvum-treated F1 hybrids between H-2 congeneic high responder (B10.A) and low responder (A) strains of mice, as well as from F1 hybrid X parent backcross animals, suggested that macrophage activation for killing of these two unrelated extracellular targets is controlled by the same autosomal dominant gene. Strains of mice that failed to develop activated macrophages after in vivo treatment with bacterial stimuli also failed to develop tumoricidal and larvicidal macrophages as a result of S. mansoni infection. The addition of antischistosome sera to the cultures did not reverse the unresponsiveness of macrophages from S. mansoni-infected C3H/HeJ, A/J, or P/N mice in in vitro larvicidal assays. Furthermore, the pattern of concomitant immunity at 6 wk after primary S. mansoni infection correlated closely with the pattern of induction of activated macrophages in these strains of mice. Whereas animals with normal macrophage function developed highly significant levels of concomitant immunity, strains with the Lps defect demonstrated lower levels of acquired resistance, and A/J and P/N mice were not significantly resistant to S. mansoni challenge infection. These results indicate that the genes controlling macrophage activation for the killing of extracellular targets also influence the development of concomitant immunity in schistosomiasis, and suggest that macrophages activated as a consequence of primary S. mansoni infection may be involved in the in vivo effector mechanism of resistance to challenge infection.

Animals↗