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Following the appearance of several antimicrobial agents to control the spread of infections, two major challenges have emerged: (i) the occurrence and blowout of multiresistant bacteria and the increase of chronic diseases and (ii) difficult‐to‐eradicate infections. In this study, we tested five benzoylthiourea derivatives for their ability to inhibit and stop bacterial growth and evaluated the possible influence of 1,2,4‐triazolyl‐benzoylthiourea derivative 4 on the formation and eradication of Staphylococcus aureus biofilms. Benzoylthiourea derivatives 4, 6, 10, 11 and 13 were obtained in one or two steps with low cost and subjected to tests to identify their minimum inhibitory concentration (MIC) and minimum bactericidal concentration. In vitro tests were also performed to assess their effects on biofilm formation and in preformed biofilms and scanning electron microscopy was used to visualize the effects on biofilm formation. The 1,2,4‐triazolyl‐benzoylthiourea derivative 4 showed bacteriostatic activity against the S. aureus HU25 clinical strain with an MIC of 16 µg ml−1, which is below the toxic concentration (at 2500 µg ml−1, 62·25% of the cells remained viable). Compound 4 also effectively prevented biofilm formation at the three subinhibitory concentrations tested (1/2 MIC, 1/4 MIC and 1/8 MIC) as confirmed by scanning electron microscopy. For breakdown of formed biofilms, the main influence was at a subinhibitory concentration (1/2 MIC). These findings make compound 4 a strong candidate for studies on the development of new antimicrobial and antibiofilm agents. [ABSTRACT FROM AUTHOR]

Keshet, a course for family members of persons’ coping with mental illness, was developed to enhance positive family cognitive communication skills. Improving communication with the use of mediation techniques, primarily used by therapists, creates a learning environment viewed as a strategy of Knowledge Translation. To examine the effectiveness of Keshet in improving attitudes, problem solving, communication skills and attenuation of burden a quasi-experimental research design was applied with study and control condition. The same group of participants (N = 38) completed questionnaires at different stages: 3 months prior to course, initiation and completion. Following participation, significant changes were observed in attitudes regarding knowledge of how to cope and interact with family member. A correlation was found between improved knowledge and decline in burden. Implementing interventions which provide caregivers with professional “know-how” leads to lessened burden, thus contributing to maintaining well-being of family caregiver population. [ABSTRACT FROM AUTHOR]

Background: A past history of major depression or alcoholism has been associated with poorer smoking treatment outcomes.Aim: To evaluate the efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism, and changes in depressive symptoms during smoking abstinence.Method: Data were drawn from a multicentre trial of bupropion for smoking cessation. Smokers (n = 615) received placebo or bupropion sustained-release at 100, 150, or 300 mg/day for six weeks after target quit date (TQD). The primary outcome was the point prevalence smoking abstinence at the end of treatment and at one year. The Beck Depression Inventory (BDI) was used to assess depressive symptoms.Results: A significant dose-response effect of bupropion for smoking cessation was found. This was independent of history of major depression or alcoholism. Among those continuously abstinent from smoking for two weeks following TQD, an increase in BDI score was associated with a return to smoking at end of treatment.Conclusions: Bupropion is efficacious for smoking cessation independently of a former history of major depression or alcoholism. Increases in depressive symptoms during an initial period of abstinence are associated with a return to smoking. [ABSTRACT FROM AUTHOR]

The quest for youth and beauty is an ongoing one. No organ conveys youth and beauty to the extent that skin does. Advances in research over the past several decades have yielded a tremendous amount of information on the molecular pathways involved in both intrinsic aging (natural) and extrinsic aging (photoaging). In this article, we aim to describe the molecular pathways that lead to an aged appearance and to describe the latest and most commonly employed drugs and procedures to reverse skin aging and stimulate the production of new collagen. With enhanced understanding of these molecular pathways, drugs and devices used to treat aging skin can be more precisely tuned. [ABSTRACT FROM AUTHOR]

Background and Purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKCepsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKCepsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception.Experimental Approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKCepsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws.Key Results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKCepsilon (PKCepsilonI) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKCepsilon, while the hypernociception induced by paw injection of PKCepsilon agonist was not affected by an inhibitor of PKA (AKAPI).Conclusions and Implications: Taken together, these findings are consistent with the suggestion that PKA activates PKCepsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception. [ABSTRACT FROM AUTHOR]

The ability of an individual to sense pain is fundamental for its capacity to adapt to its environment and to avoid damage. The sensation of pain can be enhanced by acute or chronic inflammation. In the present study, we have investigated whether inflammatory pain, as measured by hypernociceptive responses, was modified in the absence of the microbiota. To this end, we evaluated mechanical nociceptive responses induced by a range of inflammatory stimuli in germ-free and conventional mice. Our experiments show that inflammatory hypernociception induced by carrageenan, lipopolysaccharide, TNF-α, IL-1β, and the chemokine CXCL1 was reduced in germ-free mice. In contrast, hypernociception induced by prostaglandins and dopamine was similar in germ-free or conventional mice. Reduction of hypernociception induced by carrageenan was associated with reduced tissue inflammation and could be reversed by reposition of the microbiota or systemic administration of lipopolysaccharide. Significantly, decreased hypernociception in germ-free mice was accompanied by enhanced IL-10 expression upon stimulation and could be reversed by treatment with an anti-IL-10 antibody. Therefore, these results show that contact with commensal microbiota is necessary for mice to develop inflammatory hypernociception. These findings implicate an important role of the interaction between the commensal microbiota and the host in favoring adaptation to environmental stresses, including those that cause pain. [ABSTRACT FROM AUTHOR]

This is the first study to examine the outcomes in 54 patients with hematologic malignancies who received an HLA-matched related donor bone marrow (BM, n=42) or GCSF-mobilized peripheral blood stem cells (PBSC, n=12) following identical nonmyeloablative conditioning with the intention of induction of mixed chimerism (MC) followed by prophylactic donor leukocyte infusion (pDLI) to convert MC to full donor chimerism (FDC) and capture a graft-versus-tumor effect without clinical graft-versus-host disease (GVHD). Neutrophil and platelet recovery were faster and transfusion requirement was less in PBSC recipients (P<0.05). A total of 48% of BMT recipients achieved FDC with a median conversion time of 84 days, including 13 following pDLI. In contrast, 83% (P=0.04) in the PBSC group had spontaneous FDC at a median of 14 days, precluding the administration of pDLI. There was no significant difference in the incidences of acute or chronic GVHD, though the rates of chronic GVHD were considerably higher in PBSC group than in the BM group (6/7, 86% vs 10/24, 42%). CD4 and CD8 T-cell recovery was faster in PBSC recipients. In PBSC recipients, a higher number of CD34+ cells was associated with increased rates of severe, grade III–IV acute GVHD.Bone Marrow Transplantation (2007) 40, 19–27; doi:10.1038/sj.bmt.1705688; published online 30 April 2007 [ABSTRACT FROM AUTHOR]

ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and tested the effect of ABI administration on elicited antibody production in two baboons undergoing either pig hematopoietic progenitor cell (PBPC) or heterotopic heart transplantation. In vitro: Baboon peripheral blood mononuclear cells were activated in vitro to upregulate CD154, and binding of ABI to CD154 was measured by flow cytometry. In vivo: Serum levels of ABI were measured immediately before and 15 min after the intravenous administration of ABI (20 mg/kg) to two baboons over 28 days. Subsequently, ABI (25 mg/kg on days 0, 1, 4 and 7, and then 20 mg/kg every 5 days) was included in the immunosuppressive regimen in two pig-to-baboon transplants (PBPC or heart transplantation). In vitro: ABI was almost non-reactive to baboon T cells before stimulation, but bound to activated T cells. In vivo: In the pharmacokinetic study, trough levels of ABI (before the next dose) ranged between 190 and 580 lg/ml, and the estimated half-life was 10–15 days. There was no apparent toxicity. Following pig PBPC or heart transplantation, no elicited antibody was detected while ABI was being administered or during several weeks of follow-up. Conclusions: ABI functions in baboons, is well-tolerated, and prevents an elicited antibody response to pig antigens. [ABSTRACT FROM AUTHOR]

Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for α1,3-galactosyltransferase gene-knockout (GalT-KO). Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. A mean of 11 × 108 BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days 1, 2 and 4, respectively, were 641/μl (9.5%), 132/ll (3.4%), 242/ll (3.9%), and 156/ll (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (<1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved. [ABSTRACT FROM AUTHOR]

This study was conducted to examine the utility of the Activity Card Sort (ACS) as a unique assessment tool for measuring adult human occupation and level of activity. Factor analysis was used to determine whether the picture items of the ACS empirically cluster into four categories of human occupations (instrumental activities, low-demand leisure activities, high-demand leisure activities, and social activities), as well as to compare young and elderly people's classifications of activities on the ACS instrument. The study sample consisted of 184 participants who were divided into two groups (53 students and 131 elderly people). Factor analysis revealed five factors for student activities and four factors for elderly people's activities. The analysis of variance revealed that students were involved primarily in leisure activities and secondarily in independent activities of daily living (IADL), whereas elderly people were mostly involved in IADL. Pearson correlations showed the five student categories to be distinctive, whereas substantial overlapping among categories was obtained for elderly people. The use of the ACS as an important research instrument may serve to advance our understanding of the categorization of human occupations among different age groups by identifying underlying dimensions of occupational performance and assessing intensity of involvement in different occupational categories. In addition, this instrument highlights the interaction between occupational performance, person factors (various age and gender groups), and environment factors (e.g., culture). [ABSTRACT FROM AUTHOR]

The cloud radiances and atmospheric dynamics are strongly nonlinearly coupled, the observed scaling of the former from 1 km to planetary scales is prima facae evidence for scale invariant dynamics. In contrast, the scaling properties of radiances at scales < 1 km have not been well studied (contradictory claims have been made) and if a characteristic vertical cloud thickness existed, it could break the scaling of the horizontal radiances. In order to settle this issue, we use ground-based photography to study the cloud radiance field through the range scales where breaks in scaling have been reported (30 m to 500 m). Over the entire range i m to 1 km the two-dimensional (2D) energy spectrum (E(k)) of 38 clouds was found to accurately follow the scaling form E(k) ≈ k[sup -β] where k is a wave number and β is the spectral exponent. This indirectly shows that there is no characteristic vertical cloud thickness, and that "radiative smoothing" of cloud structures occurs at all scales. We also quantitatively characterize the type of (multifractal) scaling showing that the main difference between transmitted and reflected radiance fields is the (scale-by-scale) non-conservation parameter H. These findings lend support to the unified scaling model of the atmosphere which postulates a single anisotropic scaling regime from planetary down to dissipation scales. [ABSTRACT FROM AUTHOR]

Background: Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse.Objective: To evaluate the efficacy of bupropion to prevent smoking relapse.Design: Randomized, placebo-controlled trial.Participants: 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day.Intervention: The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking.Measurement: Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less.Results: The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016).Conclusions: In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TM) is a serious complication of bone marrow transplantation (BMT) that resembles thrombotic thrombocytopenic purpura (TTP). In attempting to achieve hematopoietic cell chimerism in the pig-to-baboon model, we have observed TM following infusion of high doses (>1010 cells/kg) of porcine peripheral blood mobilized progenitor cells (PBPC) into baboons. We performed investigations to analyze the pathobiology of this TM and to test therapeutic interventions to ameliorate it. PBPC were obtained by leukapheresis of cytokine-stimulated swine. The initial observations were made in two baboons that underwent a non-myeloablative regimen (NMR) prior to PBPC transplantation (TX) (group 1). We then studied three experimental groups. Group 2 (n = 2) received NMR without PBPC TX. Group 3 (n = 2) received PBPC TX alone. Group 4 (n = 6) received NMR + PBPC TX combined with prostacyclin, low-dose heparin, methylprednisolone, and cyclosporine was replaced by anti-CD40L mAb in five cases. Baboons in groups 1 and 3 developed severe thrombocytopenia (<10 000/mm3), intravascular hemolysis with schistocytosis (>10/high powered field (hpf)), increase in plasma lactate dehydrogenase (LDH) (2500–9000 U/l), transient neurologic changes, renal insufficiency, and purpura. Autopsy on two baboons confirmed extensive platelet thrombi in the microcirculation, and, similar to clinical BMT-associated TM/TTP, no unusually large vWF multimers or changes in vWF protease activity were observed in the plasma of baboons with TM. In group 2, self-limited thrombocytopenia occurred for 10–15 days following NMR. Group 4 baboons developed thrombocytopenia (<20 000/mm3) rarely requiring platelet transfusion, minimal schistocytosis (<3/hpf), minor increase in LDH (<1000 U/l), with no clinical sequelae. We conclude that high-dose porcine PBPC infusion into baboons induces a microangiopathic state with vWF biochemical parameters... [ABSTRACT FROM AUTHOR]

Objectives: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers.Design: A double-blind, placebo-controlled, dose-response trial.Setting: Multicenter (three sites) study conducted in the United States.Participants: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking.Intervention: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up).Measurements and Results: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerström Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021).Conclusion: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used. [ABSTRACT FROM AUTHOR]

Abstract: Background: Anti-Galα1–3Gal (Gal) antibodies (Gal Ab) contribute to the rejection of porcine organs transplanted into primates. Extracorporeal immunoadsorption (EIA) has been developed to eliminate Gal Ab from the circulation. Methods: Between 1995 and 1999 we performed 320 EIAs in baboons using a COBE-Spectra apheresis unit incorporating a synthetic Gal immunoaffinity column. Three plasma volumes were immunoadsorbed on each occasion. The 221 consecutive EIAs performed in 41 immuno-suppressed baboons between January 1997 and April 1999 form the basis of this review. Of these 41 baboons, 29 underwent a series of three or four EIAs at daily intervals, seven had multiple series of three EIAs, and the remainder underwent single or double EIAs. Serum Gal Ab levels were monitored by ELISA before and at intervals after the course of EIA. Results: There were two fatal complications, one from a respiratory mishap (unrelated to the EIA) and one from persistent hypotension unresponsive to therapeutic interventions. Seven procedures (3%) were terminated early owing to technical difficulties and/or persistent hypo-tension. Mean pre-EIA Gal Ab levels in naïve baboons were 33.1 µg/ml (IgM) and 14.5 µg/ml (IgG). Immediately after three consecutive EIAs, IgM was depleted by a mean of 97.3% and IgG by 99.4%. By 18 to 24 h later, Gal Ab was returning but depletion remained at 80.1% (IgM) and 84.7% (IgG). The subsequent rate of return of Gal Ab depended on the immunomodulatory protocol used. Conclusions: (1) With appropriate monitoring, EIA is an acceptably safe procedure, even in small (< 10 kg) baboons. (2) Three consecutive EIAs are effective in removing > 97% of Gal Ab. (3) In the majority of cases, return of Gal Ab begins within 24 h, irrespective of the immuno-modulatory protocol. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation after transplants between HLA-mismatched donor/recipient pairs. In mice, giving IL-2 post transplant decreases GVHD in this setting. We studied high-dose IL-2 therapy in pigs. Transplants were carried out after conditioning with fractionated total body radiation and cyclophosphamide. Fourteen pigs received a fully mismatched bone marrow transplant (six with IL-2; eight without IL-2), and six received a single haplotype class II mismatched transplant (three with IL-2; three without IL-2). GVHD was evaluated by skin histology. All fully mismatched recipients had severe GVHD (grade 2–3) and died within 13 to 51 days whether or not they received IL-2. Pigs receiving a one haplotype class II mismatched transplant without IL-2 developed severe skin GVHD lasting for 8–45 days; all died within 57 days. Similar pigs receiving IL-2 post transplant had no or only mild skin GVHD for less than 15 days; two are long-term survivors. Bone Marrow Transplantation (2000) 25, 47–52. [ABSTRACT FROM AUTHOR]

Client advocacy refers to various expressions of taking a stand such as representing and supporting the interests of clients and of populations with special needs, informing them of their rights in particular situations, making sure they have all the necessary information to make an informed decision, safeguarding their rights, and promoting legislation, policy and social awareness that may affect care and quality of life through education and public activism. The purpose of the present study is to examine situations in which occupational therapists identify the need for their involvement on behalf of clients, and identify factors that affect their behaviour when they protect, represent or inform clients about their rights. Indepth ethnographic interviews were conducted with 12 Israeli registered occupational therapists representing a variety of professional specializations and work settings. From the analysis of the results three main themes were identified as follows: a) the interviewees view themselves as 'guardians of morals' in relation to personal, professional and social misconduct, b) occupational therapists become advocates when mediation is needed to represent clients' functional abilities, and c) the role of client advocacy is affected and shaped by occupational therapists' perceptions and experiences of the interdisciplinary team. [ABSTRACT FROM AUTHOR]

We have examined the cell surface phenotype of porcine natural killer (NK) cells and compared them with classic porcine cytotoxic T lymphocytes (CTL). NK cells were susceptible to treatment with monoclonal antibodies to CD2 (PTI 1), CD8 (PT8) and Ia plus complement (C), as well as with antiserum to asialo-GM 1 (ASGM 1) plus C. In addition, monoclonal antibodies to leucocyte function antigen I (LFA-1) but not to CD8 blocked NK-mediated lysis in the absence of C. This is in contrast to porcine CTL, which were eliminated by antibodies to CD2, CD8 and Ia plus C, but not by antis ASGMI plus C, and which were blocked by anti-CD8 in the absence of C. Therefore, although porcine NK cells arc similar to porcine CTL, they are distinguished by several important differences. [ABSTRACT FROM AUTHOR]

Heterologous anti-idiotypic reagents have been prepared against a BALB/c anti-swine MHC (SLAd) monoclonal antibody (74-11-10) in order to test for possible interspecies idiotypic cross-reactions of anti-MHC antibodies. Using these reagents to examine xenoantisera produced in BALH/c mice immunized with swine SLAdd peripheral blood lymphocytes, all animals tested were found to express detectable levels of the 74-11-10 idiotype (Id). The Id could also be detected in one out of five BALB/c mice immunized with swine SLAcc PBL. Swine anti-SLAdd alloantibodies were also tested, but failed to show detectable levels of the 74-11-10 Id. The in vivo administration of anti-idiotypic reagents to BALI/c mice induced detectable levels of 74-11-10 Id positive antibodies that bound specifically to SLAdd PHL. Similar treatment of SLAgg swine (recombinant swine expressing the class I MHC molecules of c) with anti-idiotypic antibodies failed to induce anti-SLAd antibody activity. These results thus indicate that 74-11-10 represents a shared idiotype of BA LB/c anti-SLAdd antibodies. The presence of 74-11-10 Id in one mouse immunized with SLA∞ PBL suggests that the failure of pigs to express the 74-11-10 Id following treatment with anti-idiotypic antibodies may be the result of tolerance rather than absence of the relevant variable region gene(s). [ABSTRACT FROM AUTHOR]

MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (APC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8 4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function, EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coated petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 X 10[SUP7] TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous immunity in a manner similar to Langerhans cells in murine or human skin. [ABSTRACT FROM AUTHOR]

After mice of several inbred strains were injected with Listeria monocytogenes, two parameters of resistance, the 50% lethal dose and the suppression of bacterial proliferation in spleen, were determined. The strains of mice tested could be segregated into two groups: the resistant C57BLjlOSn mice and the sensitive AIJ and DBAj2J mice. Congenic resistant strains of mice were used because they would express the H-2 haplotype of the sensitive strains (H-2a or H-2d) on the background of a resistant strain, C57BL/10Sn. Both the B10A/SgSn (H-2a) and the B10.D2/Sn (H-2d) mice were as resistant as mice from their background strain and were significantly more resistant than the strains that donated their H-2 locus (A/J or DBA/2J). Therefore, the resistance of mice to Listeria, although genetically controlled, is not controlled by gene (s) linked to the H-2 haplotype. On the other hand, the level of specific immunity to listeria antigens (as indicated by the footpad reaction) was higher in the C57BL/10Sn (H-2b) mice than in either the A/J and B10.A/SgSn (H-2a) mice or the DBA/2J and B10.D2/Sn (H-2d) mice. This observation suggests an H-2 linkage of specific immunity to Listeria. [ABSTRACT FROM PUBLISHER]

This study evaluated serum nicotine and sensory differences of five different doses of nicotine polacrilex (0.0, 0.5, 1.0, 2.0 and 4.0 mg nicotine), three of which have been used as placebo doses in clinical trials (0.0, 0.5, and 1.0 mg) and two of which are currently available as pharmacologic treatments for smoking cessation (2.0 or 4.0 mg nicotine). Twenty-one smokers received, on different days and in random order, five pieces of each of the five doses of polacrilex. The objective of the study was to evaluate whether consistent serum nicotine and sensory differences would be observed between the doses. After 5 h use, the 0.0, 0.5, 1.0, 2.0, and 4.0 mg doses produced the following results: (1) there was a linear trend across the placebo doses of nicotine polacrilex in serum nicotine and nicotine flavor, although pairwise dose comparisons were not significant, (2) the 0.0 and 0.5 mg placebo doses resulted in serum nicotine and sensory ratings that were significantly different from the 2.0 mg dose, and even more so from the 4.0 mg dose, (3) the 1.0 mg dose was not different from the 2.0 mg dose on serum nicotine level and several sensory characteristics, though it was different from the 4.0 mg dose on both, and (4) the 4.0 mg dose resulted in significantly higher serum nicotine and usually higher sensory ratings than the 2.0 mg dose. Since the 0.0 mg placebo achieves sensory effects that are comparable to the nicotine-containing placebo doses, it is recommended over the 0.5 and 1.0 mg doses as the nicotine polacrilex placebo of choice in most clinical trials. [ABSTRACT FROM AUTHOR]

Murine peritoneal cells, both induced and noninduced, were examined for Ia antigens by a variety of techniques. Complement-mediated cytotoxicity and indirect immunofluorescence, analyzed by both visual microscopy and the fluorescence-activated cell sorter, detected Ia antigens on the surface of an average of 8% to 15% of cells with the morphologic and functional characteristics of macrophages. Internal radioisotope labeling studies showed that these antigens were actually synthesized by the macrophages. The antigens were borne on molecules which consisted of two components with apparent molecular weights of roughly 33,000 and 25,000 daltons. At least some of those molecules existed as a two-chain structure of 58,000 daltons linked by disulfide bonds. Although macrophage Ia antigens appeared to be structurally similar to the Ia antigens found on spleen cells, the radioisotope labeling studies indicated that the quantity of labeled Ia-bearing molecules isolated from peritoneal macrophages was at most 1/15 that found for B lymphocytes. In addition. anti-Ia antisera failed to inhibit the binding of heat-aggregated immunoglobulin to the Fc receptor of macrophages. Thus, Ia antigens appear to be present at very low levels in macrophage populations, similar to the low levels of Ia antigens found in T-lymphocyte populations. These studies suggest that Ia antigens exist on only a subpopulation of peritoneal macrophages. Alternatively, all cells in the population might bear small amounts of Ia antigens with only a fraction having sufficient numbers of molecules to be detected by the assay systems used. [ABSTRACT FROM AUTHOR]