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HESS J0632+057 belongs to a rare subclass of binary systems which emits gamma-rays above 100 GeV. It stands out for its distinctive high-energy light curve, which features a sharp ``primary'' peak and broader ``secondary'' peak. We present the results of contemporaneous observations by NuSTAR and VERITAS during the secondary peak between Dec. 2019 and Feb. 2020, when the orbital phase ($\phi$) is between 0.55 and 0.75. NuSTAR detected X-ray spectral evolution, while VERITAS detected TeV emission. We fit a leptonic wind-collision model to the multi-wavelength spectra data obtained over the four NuSTAR and VERITAS observations, constraining the pulsar spin-down luminosity and the magnetization parameter at the shock. Despite long-term monitoring of the source from Oct. 2019 to Mar. 2020, the MDM observatory did not detect significant variation in H$\alpha$ and H$\beta$ line equivalent widths, an expected signature of Be-disk interaction with the pulsar. Furthermore, fitting folded Swift-XRT light curve data with an intra-binary shock model constrained the orbital parameters, suggesting two orbital phases (at $\phi_D = 0.13$ and 0.37) where the pulsar crosses the Be-disk, as well as phases for the periastron ($\phi_0 = 0.30$) and inferior conjunction ($\phi_{\text{IFC}} = 0.75$). The broad-band X-ray spectra with Swift-XRT and NuSTAR allowed us to measure a higher neutral hydrogen column density at one of the predicted disk-passing phases., Comment: 21 pages, 9 figures, accepted to ApJ

Background Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. Materials and methods Patients’ DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg−1 of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated. Results The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses. Conclusions Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.

Understanding the impact of effective paediatric adherence promotion interventions on patients, families and the healthcare system is necessary to inform efforts to improve healthcare quality and control costs. Building on previous research suggesting that improving adherence may have far-reaching benefits, the objective of this study was to quantify the impact of effective adherence promotion interventions for children and adolescents with a chronic medical condition on patients, families and the healthcare system.Authors systematically reviewed articles indexed in PubMed, PsycINFO and CINAHL to identify randomized controlled trials of paediatric adherence promotion interventions. Interventions that improved paediatric adherence and examined patient-level, family-level or healthcare system-level outcomes in children and adolescents (M age ≤ 18 years) with a chronic medical condition were included. Two authors independently extracted and classified outcome variables as patient-level (quality of life and disease-related activity restrictions), micro-level (family functioning, family conflict, caregiver quality of life, caregiver sleep interruption, caregiver days away from work and patient missed school days) or macro-level variables (emergency department visits, hospitalizations, outpatient visits and urgent care visits). Outcome variables detailed in previously published reviews (i.e. disease severity) were excluded.Twenty studies representing 19 unique samples met inclusion criteria. An additional eight articles representing trials that did not significantly improve adherence were included in post hoc analyses. Compared with control interventions, effective paediatric adherence promotion interventions improved patient quality of life and family-level outcomes and decreased healthcare utilization among children and adolescents with a chronic medical condition.Interdisciplinary efforts to improve healthcare quality and reduce spending among children and adolescents with a chronic medical condition may be enhanced by incorporating effective paediatric adherence promotion interventions. As relatively few chronic medical conditions were represented in included studies, future research should examine the impact of paediatric adherence promotion interventions in other populations.

We have studied the in vitro activation of murine lymphocytes with LPS incorporated in the membranes of both phospholipid vesicles (liposomes) and vesicles composed of fusogenic, reconstituted influenza virus envelopes (virosomes). The incorporation of Salmonella minnesota rough-LPS in liposomes reduced the potency of LPS to stimulate splenocyte proliferation and cell surface kappa-light chain expression on 70 Z/3 pre-B cells by over 100-fold. Salmonella minnesota rough-LPS inserted into virosomes was at least 10-fold more potent than free LPS, both when prebound virosomes were allowed to be taken up by the cells at neutral pH and when the virosomes were fused into the plasma membrane by low pH treatment. Inactivation of the virosomes by low pH pretreatment reduced the potency of the virosomal LPS to the level of liposome-incorporated LPS. The association of the various LPS forms with the cells was quantitated using radio-iodinated LPS. Correcting for uptake, virosomal LPS remained 2- to 10-fold more potent than free LPS in stimulating B lymphocytes and at least 100-fold more active than liposomal LPS or fusion-inactivated virosomes. After low pH-induced fusion with the plasma membrane, the majority (80%) of the prebound virosomes had fused with the cells, compared with about 8% after neutral uptake. From these results we conclude that LPS inserted into the plasma or endosomal membranes efficiently activates murine lymphocytes. The fusion data suggest that the incorporation into endosomal membranes might be a more effective stimulus.

Objective -To study the acquisition of tobacco and the development of cigarette brand selection among youth. To com pare four methods of measuring brand preference among underage smokers. Design - Individual interviews were con ducted with youths to elicit their past and present experiences with tobacco. Setting - A high school and public places in Massachusetts, USA. Subjects-A convenience sample of 721 youths, aged 10-17 years. Results - Friends were the source of the subject's first cigarette in 69 % of cases. Fifty per cent of the subjects were smoking three or fewer cigarettes per day when they first purchased tobacco. The first brand smoked was the first regular brand chosen in 67 % of cases, and 51 % of smokers were still smoking the same brand as their first cigarette. Ultra-low tar and generic brands were unpopular among youths. Questions concerning the favourite brand, brand usually pur chased, last brand smoked, and friend's favourite brand produced very similar brand preference results for full-priced brands. However, only the question con cerning the last brand smoked seemed to assess the use of generic brands accu rately.

Hepatitis B virus infection is preventable by vaccine and the correlate of immunity is the induction of antibody. The 2.5 μg antigen per dose of H-B-VAX II given in appropriate regimens is adequate to immunize normal newborn infants and children up to 11 years of age. A 5 μg dose may be needed to protect newborn infants born to mothers who are carriers of hepatitis B infection and should be used when the carrier status is either positive or is unknown. The immune response in newborn infants is usually of lower titre than in infants who are 2–3 months of age or older. The level of protection afforded in otherwise healthy individuals by plasma-derived vaccine is high and lasts for longer than 7 years, even though the level of circulating antibody may have declined to a less than detectable amount. A similar pattern of antibody decline follows administration of recombinant vaccine. The mechanism for sustained protection is in long-term immunological memory with rapid recall of antibody production on exposure to the virus in nature. Administration of hepatitis B vaccine will be simplified by combination with DPT and poliomyelitis vaccines in single-dose formulations that are under current development. An experimentally killed hepatitis A virus vaccine prepared by formaldehyde inactivation of attenuated live virus purified from infected MRC-5 cell cultures induces rapid and high level antibody response when the vaccine is given in as little as 100 ng of antigen per dose and in two- or three-dose regimens. The vaccine is highly protective when assayed in challenge studies in animals and the levels of antibodies achieved are far in excess of those provided by immune globulin when used for passive protection in humans. Field investigations to demonstrate protective efficacy against natural challenge in human beings have been in progress and protective efficacy has been established.

The current study investigated whether differences existed in health-related quality of life between individuals who self-identified as having childhood-onset asthma and individuals without a chronic illness. Additionally, the relationship between perceived illness intrusiveness and illness uncertainty to health-related quality of life was explored.College undergraduates at least 18 years of age who self-identified as having childhood asthma were randomly matched by age and gender to healthy control participants. Participants completed a demographic form, the Mishel Uncertainty in Illness Scale-Community Form, the Illness Intrusiveness Scale, and the SF-36 Health Survey, a measure of health-related quality of life.Participants with asthma had significantly lower scores on the total and mental health-related quality of life scales than did healthy control subjects. There were no significant differences between self-identified participants with asthma and matched healthy control subjects on physical health-related quality of life scales. Illness intrusiveness was not related to either the physical (e.g., physical functioning, general health) or mental health-related quality of life. Higher levels of illness uncertainty were significantly related to higher levels of mental health-related quality of life (e.g., vitality, mental health). In addition, participants with asthma scored significantly lower than healthy controls on the social functioning and role-emotional subscales.The current study adds to the extant literature by examining the relationships between illness intrusiveness, illness uncertainty, and health-related quality of life among a young adult population. College students with asthma appear to be at risk for diminished quality of life compared to a healthy comparison group. Further examination of various domains of health-related quality of life among older adolescents and young adults with childhood asthma is needed.

The stimulated murine macrophage was found to contain 11 major gangliosides of which 8 were determined to be monosialylated. The thin-layer chromatographic patterns were complicated by the presence of both sialic acid and ceramide fatty acid heterogeneity. N-glycolyl and N-acetylneuraminic acid-containing species were present for each ganglioside characterized. Although C18 sphingosine was the only long chain base detected, ceramide fatty acid ranged from C16 to C24 carbon moieties. Based on gas-liquid chromatographic and antibody analyses, all major tetraosyl structure gangliosides were ganglio series types. Comprising 43 to 60% of thioglycollate-stimulated cells and 60 to 70% of Escherichia coli-activated cells, monosialosyl-gangliotetraosyl ceromides (Gm1 gangliosides) were the major monosialo species of which four were present: sialidase-resistant NeuGc-GM1a and NeuAc-GM1a and sialidase sensitive NeuGc-GM1b and NeuAc-GM1b. Analyses of thioglycollate-elicited murine peritoneal macrophage ganglioside patterns from four strains of mice, including the C3H/HeJ strain, indicated that, in the absence of any expression of a genetic defect, the pattern is conserved. However, when E. coli was used as the activating agent, the normal C3H/HeN macrophage contained little Gm1a with the sialidase-sensitive Gm1b predominant; the converse was true for the congenic endotoxin hyporesponsive C3H/HeJ strain. Therefore, C3H/HeJ mice are not defective in ganglioside metabolism per se but in the processing of an endotoxin stimulus such that one manifestation is an altered macrophage ganglioside pattern deficient in Gm1b.

Endotoxin-responsive (C3H/HeN) and -hyporesponsive (C3H/HeJ) murine B lymphocytes purified by adherence to anti-immunoglobulin ("antibody panning") possess identical gangliosides but different ganglioside surface accessibilities. We investigated the distribution and surface accessibility of gangliosides of B lymphocytes purified by adherence to plastic ("plastic panning") or by subtraction of non-B-lymphocyte components. As with antibody panning, there were no entirely new or absent gangliosides in plastic-panned or subtraction-purified B lymphocytes of each strain. However, striking changes in relative expression of five gangliosides were detected with each purification protocol. Moreover, five gangliosides of antibody-panned and plastic-panned B lymphocytes but only two gangliosides of subtraction-purified B lymphocytes were inaccessible to surface labeling. Unlike the situation for antibody-panned B lymphocytes, no interstrain (HeN vs. HeJ) surface accessibility differences existed in gangliosides of plastic-panned or subtraction-purified cells. Exposure of subtraction-purified B lymphocytes to anti-immunoglobulin failed to elicit changes in ganglioside expression. Murine B lymphocytes have distinct protocol-dependent differences in glycolipid phenotype which likely denote individual subpopulations.

Evidence from in vitro experiments and animal and human studies indicate that antibiotic therapy may induce the release of endotoxin from the outer membrane of Gram-negative bacteria. Antibiotics that bind preferentially to penicillin-binding protein-2 (PBP-2)--such as imipenem--are associated with little release of endotoxin, while antibiotics that preferentially bind to PBP-3--such as ceftazidime--are associated with far greater release of endotoxin. We conducted a randomized, multicenter, double-blind study comparing imipenem to ceftazidime in patients with urinary tract infections caused by Gram-negative bacilli associated with signs and symptoms of systemic inflammation. A total of 33 patients were randomized to receive either imipenem (n = 14) or ceftazidime (n = 19) for initial treatment for urosepsis. No differences in plasma endotoxin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) or urine endotoxin, IL-6 or IL-8 levels were found between the two treatment groups within the first 8 h after antibiotic administration. We conclude that, if differences exist with respect to endotoxin release by these two antimicrobial agents, these differences are not readily demonstrable in this clinical study with carefully defined patients with Gram-negative urinary tract infections.

Interleukin-12 (IL-12) is a key regulator of cell-mediated immunity that has therapeutic potential in cancer and infectious disease. In a previous Phase 1 dose escalation study of a single test dose of recombinant human IL-12 (rhIL-12) followed 14 days later by cycles of five consecutive daily intravenous injections every 3 weeks, we showed that a dose level up to 500 ng/kg could be administered with acceptable levels of safety. Based on these results, a Phase 2 study was conducted. In the Phase 2 study, however, administration of rhIL-12 at this same dose level resulted in severe toxicities with some patients unable to tolerate more than two successive doses. Of the 17 patients receiving rhIL-12 in the Phase 2 study, 12 patients were hospitalized and two patients died. A thorough scientific investigation to determine the cause of this unexpected toxicity failed to identify any difference in the drug products used or the patient populations enrolled in the Phase 1 and Phase 2 studies that could have accounted for the profound difference in toxicity. The focus of the investigation therefore shifted to the schedule of rhIL-12 administration. We determined that a single injection of rhIL-12 2 weeks before consecutive dosing included in the Phase 1 study, but not in the schedule of administration in the Phase 2 study, has a profound abrogating effect on IL-12-induced interferon-gamma (IFN-gamma) production and toxicity. This observation of schedule-dependent toxicity of IL-12 has been verified in mice, as well as nonhuman primates. In this regard, a single injection of IL-12 before consecutive daily dosing protected mice and cynomolgus monkeys from acute toxicity including mortality and was associated with an attenuated IFN-gamma response. Because of this unique biologic response, careful attention to the schedule of administration is required to assure safe and effective clinical development of this highly promising cytokine.

L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm 3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT >100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds

A central theme for EMS systems is the reduction of death and disability from emergency illnesses and injuries, with most systems focusing exclusively on treatment to fulfill their missions. Unfortunately, this has often resulted in the neglect or complete disregard of prevention, which actually may be the more powerful intervention strategy. Yet hopefully, as EMS systems begin to learn and embrace the principles of continuous quality improvement (CQI) in their organizational cultures, the advantages of prevention vs. treatment will become more apparent and internally recognized.

Peritoneal macrophage ganglioside patterns and ganglioside sialic acid content were compared for two congenic strains of mice having differing responses to bacterial lipopolysaccharide. Resident macrophage ganglioside patterns from C3H/HeJ mice (endotoxin hyporesponsive) and C3H/HeN mice (endotoxin responsive) were similar. Macrophages elicited with phenol-extracted or butanol-extracted endotoxin showed distinctly more complex ganglioside patterns in C3H/HeN mice. C3H/HeJ macrophages showed distinct, but less complex changes when elicited with butanol-extracted endotoxin. As expected, there were minimal alterations induced by phenol-extracted endotoxin in the C3H/HeJ patterns. When injected with whole killed E. coli, both strains of mice exhibited complex ganglioside patterns; however, there were relative differences in the quantities of multiple gangliosides. Differences in ganglioside patterns were mirrored in the relative ratios of N-acetyl- to N-glycolylneuraminic acid. When macrophages were activated by administration of either endotoxin preparation, macrophage gangliosides from C3H/HeN mice always contained a higher proportion of N-acetylneuraminic acid compared with C3H/HeJ macrophage gangliosides. Oxidative metabolism of the macrophage populations was assessed by PMA-induced H2O2 release. This indicated that endotoxin activation produced an increase in PMA-induced H2O2 release as well as a shift of sialic acid class from the N-glycolyl type to the N-acetyl type. However, no direct correlation could be made between ganglioside composition, sialic acid content, and macrophage function. These data indicate that both ganglioside composition and sialic acid composition of macrophages are profoundly altered with endotoxin activation. The data further indicate that under conditions which C3H/HeJ mice respond to Gram-negative bacteria, their macrophage ganglioside patterns still differ from normal mice.

In an attempt to define the mechanism by which endotoxin induces its biological activity, we studied the effect of the incorporation of lipopolysaccharide and lipid A into phospholipid vesicles (liposomes) on the stimulation of the macrophage cell-line RAW 264.7 and on the coagulation of Limulus amoebocyte lysate. The incorporation of Salmonella minnesota smooth-and rough (Re) lipopolysaccharide or primarily monophosphoryl lipid A into multilamellar and small unilamellar vesicles consisting of phosphatidylcholine, phosphatidylserine and cholesterol (molar ratio 4:1:4) reduced the interleukin 1 inducing potency of these substances about 1000-fold. When corrected for the actual uptake of radiolabeled free and liposome-incorporated lipopolysaccharide by the cells, this difference amounted to 100- to 1000-fold. In addition, liposome-associated Re-lipopolysaccharide was about 1000-fold less potent in stimulating the Fc-receptor mediated uptake of IgG-coated sheep erythrocytes by the cells. The ability of lipopolysaccharide and lipid A to coagulate the Limulus amoebocyte lysate appeared to be at least 100-fold decreased upon incorporation into phospholipid vesicles. Control experiments demonstrated that liposomes prepared without lipopolysaccharide did not reduce the studied activities of free lipopolysaccharide. In conclusion, the incorporation of lipopolysaccharide into the liposomal membrane probably prevents the interaction of the hydrophobic portion of the lipid A component of lipopolysaccharide with the plasma-membrane structures involved in the activation of macrophages and with the proteins of the Limulus amoebocyte lysate. This indicates that the direct interaction of the lipid A moiety of lipopolysaccharide with the macrophage plasma-membrane is required to optimally trigger the studied responses.

The rate of glucose utilization has been used as a measure of LPS-induced activation of cultures of C3H/HeN and C3H/HeJ spleen cells, peritoneal cells, and purified peritoneal adherent cells. Peritoneal cells utilized 40 to 60 times more glucose than did spleen cells and purified adherent monolayers were more active than mixed peritoneal cells, suggesting that only macrophage metabolism was being measured. The cell preparations for C3H/HeJ mice were not activated by Escherichia coli K235 LPS prepared by extensive phenol extraction, whereas C3H/HeN cells were activated by that LPS. Cells from both strains were activated by a commercially obtained E. coli 0111:B4 LPS and butanol-extracted K235 LPS. The addition of 10% C3H/HeN spleen cells to C3H/HeJ peritoneal cells resulted in a marked enhancement of glucose utilization. These findings suggest that LPS-induced enhancement of macrophage metabolism occurs both by direct action of LPS on macrophages as well as indirectly through activated lymphocytes.

Lymphocytes, activated by lectins or specific antigens, have been shown to enhance macrophage phagocytosis through the elaboration of a heat-labile soluble factor(s). Recent evidence from our laboratory revealed that resident (nonactivated) murine thymocytes and splenic lymphocytes increase peritoneal macrophage glucose metabolism through the elaboration of a heat-stable soluble factor(s). Therefore, we investigated the effect of resident lymphocyte subpopulations on macrophage Fc-dependent phagocytosis. Thioglycollate-elicited and resident peritoneal macrophages from BALB/c mice were cultured in serum-free media with syngeneic resident thymocytes or splenic T lymphocytes. Macrophage Fc-dependent phagocytosis was assayed by measuring the ingestion of 51CrSHEA. After 4 days in vitro, resident thymocytes produced a mean 160 (+/- 31) and 136% (+/- 22) increase in Fc-dependent phagocytosis by thioglycollate-elicited (thio-macrophages) and resident peritoneal macrophages, respectively. Splenic T lymphocytes increased thio-macrophage phagocytosis by 112% (+/- 41) under similar conditions. Macrophage Fc-dependent phagocytosis was increased after 24 hr of co-culture by supernatant derived from resident thymocytes and could be further enhanced by supernatant from Con A-activated thymocytes. Supernatant from guinea pig embryo fibroblasts did not increase macrophage phagocytosis. The soluble factor(s) was produced by resident thymocytes after 24 hr of preculture. This factor was active despite heating at 100 degrees C for 30 min whereas the effect of Con A-activated thymocyte supernatant was heat-labile. The stimulatory effect of resident thymocyte supernatant was not observed when the macrophages and supernatant were cultured in 2% FCS. In contrast to the factor(s) produced by resident thymocytes, the factor(s) in FCS that increased phagocytosis was heat-labile. These data suggest thymocytes and splenic T lymphocytes promote macrophage Fc-dependent phagocytosis in the absence of antigenic or lectin stimulation. This previously unrecognized effect of resident thymocytes is due to a unique heat-stable soluble factor(s) that is concealed in the presence of serum.

Immobilized antigen-antibody complexes are able to inhibit the mitogenic response of murine spleen cells to the B-cell mitogen 8-bromo-3',5'-cyclic guanosine monophosphoric acid. This this inhibition is dependent on intact Fc fragments in the immobilized complexes. Soluble complexes do not mediate this inhibition. When lipopolysaccharide (lps) activation of B cells was studied, it was found that the mitogenic response was inhibited at all times tested between 2 and 7 days of culture. Also, the LPS-induced mitogenesis of nude spleen cells was inhibited by immobilized complexes, indicating that suppressor T cells probably play no significant role in the inhibition. Immobilized complexes inhibit polyclonal antibody responses in a serum-free system and in the presence of normal mouse serum, but are unable to inhibit in the presence of fetal calf serum (FCS). If nu/nu spleen cells are used, however, the FCS does not block the ability of the complexes to inhibit the polyclonal response. It is suggested that that antigen-antibody complexes under appropriate conditions may bind to B lymphocytes via their Fc receptors and trigger a central "off" signal which blocks proliferation and consequently antibody production.

In the present study, responses stimulated by phenol-extracted lipopolysaccharide (LPS(phenol)) and butanol-extracted LPS (LPS(butanol)) were used to assess the possibility that xid B cells might not be identical to the Lyb-5- B cells present in normal mice. It was found that xid B cells responded well only to LPS(butanol) whereas normal B cells responded well to both LPS(butanol) and LPS(phenol). Thus, LPS(butanol) appeared to be a TI-1 antigen and LPS(phenol) appeared to be a TI-2 antigen. In contrast to classical TI-2 responses, however, responses stimulated by LPS(phenol) did not exhibit a stringent requirement for accessory cells. Furthermore, if LPS(phenol) were a classical TI-2 antigen, it should only activate Lyb-5+ B cells. To determine if the responsiveness of normal B cells to LPS(phenol) were due, at least in part, to the stimulation of normal Lyb-5- B cells, the responsiveness of normal neonatal B cells and normal adult B cells that had been pretreated with anti-Lyb-5.1 + C was assessed. It was found that both normal neonatal B cells and normal adult Lyb-5- B cells did respond well to LPS(phenol). Thus, even though LPS(phenol) does not stimulate xid B cells, these data demonstrate that LPS(phenol) is different from other TI-2 antigens. More importantly, these data also demonstrate that xid B cells and normal Lyb-5- B cells are not identical. It is hypothesized that the normal Lyb-5- B cell subpopulation is heterogeneous, consisting of an Lyb-5(1)- and an Lyb-5(2)-B cell subset with the xid mutation blocking the differentiation of Lyb-5(1)-B cells into Lyb-5(2)-B cells.

The proteins expressing interleukin 1 (IL 1) activity from rat peritoneal macrophages and cultured glomerular mesangial cells were compared after purification to apparent homogeneity. The purified IL 1 shared a number of biochemical features including m.w., charge, and specific activity. These findings were extended by the results of proteolytic peptide mapping, which revealed similar breakdown oligopeptides, confirming the close resemblance of these two IL 1 species produced by macrophages and mesangial cells. The purified mesangial cell IL 1 acts as an autocrine or paracrine growth factor. The local release of this cytokine may be an important factor in glomerular diseases characterized by mesangial proliferation and matrix expansion.

Macrophage phagocytic activity is regulated in part by products of activated T lymphocytes. We previously reported that a heat-stable soluble factor derived from resident (nonactivated) thymocytes increases murine peritoneal macrophage Fc-dependent phagocytosis. In the present study, we further investigate the effect of the thymocyte factor on immune and nonimmune receptor-mediated phagocytosis, Fc receptor expression, and its approximate m.w. After 4 days of incubation, cellfree thymocyte supernatant produced a mean (three experiments) 2.10-, 2.08-, and 1.97-fold increase in macrophage phagocytosis of C3-, IgG-, and tannic acid-treated erythrocytes, respectively. Macrophage IL 1 production was not enhanced by a similar concentration of thymocyte supernatant. The thymocyte factor(s) increased the number of IgG2a Fc receptors (FcRI) from 2.4 x 10(5) to 3.8 x 10(5) receptor sites per macrophage. The number of Fc receptors that bind IgG1 and IgG2b (FcRII) was not altered. The soluble factor(s) that increased Fc-mediated phagocytosis passed through both 6000- to 8000-dalton and 2000-dalton cutoff dialysis membranes and eluted from a Sephadex G-25 Fine column over a m.w. range of 200 to 1000 daltons, with a peak activity at 450 daltons. These data suggest that resident thymocytes enhance macrophage phagocytosis of opsonized and nonopsonized particles through the elaboration of a low m.w. substance(s).

Mouse spleen cells, cultured on surfaces coated with antigen-antibody complexes, are inhibited from responding to the B-cell mitogens, lipopolysaccharide, lipid A, Pneumococcal polysaccharide SIII, and poly I:C. The response to the T-cell mitogen, concanavalin A, is also substantially inhibited by immobilized antigen-antibody complexes, but specific inhibition of the response to phytohemagglutinin is minimal. Control experiments showed that immobilized complexes prepared from IgG F(ab')2 fragments and IgA antibodies (both of which fail to bind to Fc receptors when complexed to antigen) did not show significant inhibitory activity when compared with the inhibition observed with complexes prepared from whole IgG. Suspensions of antigen-antibody complexes prepared from the same antigen and intact IgG antibody did not inhibit mitogenesis. None of the mitogens used could be demonstrated to compete with the binding of aggregated immunoglobulin to the B-cell Fc receptor. It appears that the interaction of Fc receptor-bearing lymphocytes and/or macrophages with immobilized complexes prevents lymphocyte activation by mitogens. It is suggested that the mechanism(s) involved may be relevant to antibody feedback control of the humoral immune response.

Fully acetylated diamines hexamethylenebisacetamide (HMBA) and diacetylputrescine (tetramethylenebisacetamide, TMBA) cause inhibition of murine B lymphocyte activation in the absence of ruminant serum. Mitogenesis induced by LPS, LAP, and 8-BrcGMP was profoundly inhibited in the presence of 3 mM HMBA and TMBA. PHA-stimulated thymidine uptake was not affected. Higher levels of the acetylated polyamines were toxic to lymphocytes. Immunoglobulin secretion by LPS-stimulated spleen cells was inhibited in similar fashion. This inhibition requires the early addition of the polyamines and does not appear to be associated with direct inhibition of DNA synthesis. These data support the hypothesis that polyamines represent immunomodulatory agents and suggest that acetylated derivatives of polyamines may also have activity in regulating B lymphocyte activation.

The oxygen and glucose metabolism of peritoneal macrophages harvested from untreated mice (resident cells) and mice given an i.p. injection of thioglycollate broth (thioglycollate cells) were examined. Thioglycollate cells consumed approximately 3 times as much O2 at rest and during phagocytosis as resident cells, but oxygen reduction products (superoxide and hydrogen peroxide) could be recovered in only minimal amounts despite triggering by phagocytosis or exposure to PMA. Indirect evidence for the formation of oxygen reduction products such as O2- by thioglycollate cells was obtained by observation of the major pathways for glucose oxidation and NBT dye reduction. When thioglycollate cells were allowed to adhere to a glass surface O2- and H2O2 were easily recovered in the extracellular medium with a 20-fold increase above cells in suspension exposed to PMA. This study suggests that thioglycollate-elicited macrophages have a vigorous oxidative metabolism but that recovery, and perhaps utilization, of O2 reduction products formed will depend on the conditions of incubation. These events may be significant both for the study of parameters of macrophage "activation" in vitro as well as the function of these cells in vivo.

Conditioned media from LPS-activated rat peritoneal macrophages enhanced the proliferation rates of cultured rat glomerular mesangial cells. This macrophage-derived activity extensively co-purified with interleukin 1 (IL 1) activity through sequential ammonium sulfate precipitation, S-200 gel chromatography, DEAE-cellulose anion exchange chromatography, and phenyl-Sepharose chromatography. In addition, the macrophage-derived factor was heat-labile (80 degrees C) and inactivated by phenylglyoxal, thus allowing tentative identification as IL 1. Macrophage supernatants and purified IL 1 enhanced the proliferative rates of mesangial cells only in the presence of serum; the use of platelet-poor plasma or serum depleted of platelet-derived growth factor was without effect. IL 1 acted to increase the percentage of cycling cells, without a change in the length of the individual cell cycle times. These findings provide a potential mechanism whereby activated macrophages, in combination with platelet factors, enhance mesangial cell proliferation. Such processes may contribute to the mesangial hypercellularity frequently found in immune-mediated glomerulonephritis.

The glomerular mesangium is centrally involved in immune-mediated glomerulonephritis. The mesangial cell is a mesenchyme-derived multipotential vascular pericyte, which shares several properties with macrophages. Cultured, proliferating rat mesangial cells produce a factor, mesangial cell-derived thymocyte-activating factor (MC-TAF), which physicochemically and biologically closely resembles macrophage interleukin 1. MC-TAF is heat labile, of low m.w. (approximately 15,000), and adheres to anion exchangers. MC-TAF acts to augment lectin-induced thymocyte proliferation and enhances peripheral lymphocyte production of interleukin 2. These findings suggest that a mesangial cell cytokine may interact with the cellular immune system in an antigenically nonspecific fashion to modulate immune responses in glomerular disease.

A simple, effective method is needed for growing obligate anaerobes in the clinical laboratory. This report describes a pre-reduced anaerobic bottle that can be taken to the bedside for direct inoculation, provides a flat agar surface for evaluation of number and morphology of colonies, and can be incubated in conventional bacteriological incubators. Each anaerobic culture set consisted of two bottles containing brain heart infusion agar and CO 2 . Gentamicin sulfate (50 μg/ml) was added to one of these to inhibit facultative enteric bacilli. Comparison of the anaerobic bottles with an identical aerobic bottle which was also routinely inoculated permitted early identification of anaerobic colonies. Representative species of most anaerobic genera of proven pathogenicity for man have been isolated from this system during 10 months of routine use.

The optical absorption spectrum of single crystal [(C2H5)4N]2NpCl6 has been examined. Between 300 and 77°K the spectrum can be understood in terms of the analysis made recently for Cs2NpCl6 since many aspects of the NpCl6 complex spectrum are similar. At 4°K, however, the spectrum shows evidence for two inequivalent sites of Np4+. The octahedral ground state Γ8 is split by 14 cm−1 in one site and by 16.5 cm−1 in the other site. The reason for occurrence of inequivalent sites in the salt is attributed to Jahn‐Teller instability coupled with the presence of the large organic complex cation [(C2H5)4N]+.

Locomotives are often built and maintained in kind for their service life, renewal parts being made according to their original design, whereas at but little if any additional cost, they might be renewed to modern design and proportions. In this paper the author discusses the high percentage of the total number of steam locomotives having road assignment which do not have modern proportions and which will be continued in service for many years. This situation leads to the suggestion that increased capacity and economy may be built into them at slight additional expense by following the practice of making required maintenance renewals according to modern proportions, with particular emphasis on adequate steam space, increased gas area through the boiler, a high degree of superheat, and valve events for speed and capacity.

The anion-exchange absorption of the quadrivalent actinides is compared with spectrophotometric and solubility data. The plutonium, neptunium, and uranium species absorbing on anion exchangers from nitric acid and from calcium nitrate are Pu(NO/sub 3/)/sup 2-//sub 6/ Np(NO/sub 3/)/sup 2-//sub 6/, and U(NO/ sub 3/ )/sup 2-/ The data indicate that in the case of thorium, Th(NO/sub 3/)/sup 2-//sub 6/ is absorbed. The presence of distinct maxima in the anion exchange distributions of the quadrivalent actinides in nitric acid is attributed to the formation of HM(NO/sub 3/)/sup -//sub 6/ and H/sub 2/M(NO/sub 3/)/sub 6/ at high acidity. The marked similarity between anion exchange of metal complexes and the solubility of quaternary amine salts of these complexes is pointed out. (auth)

The site symmetry of Nd3+ in single‐crystal [(C6H5)3PH]3NdCl6 is predicted by considerations of molar absorptivity, vibronic spectra, and stoichiometry. A calculation of the crystalline‐field splitting of 4f3 J levels appears to predict a sixfold octahedral site symmetry with a slight distortion along one of the axes, in agreement with the observed spectrum. In addition, the observed spectrum indicates the occurrence of two slightly inequivalent sites of Nd3+. The effects of the small distortion away from octahedral symmetry and the spectrum due to two inequivalent sites are sufficiently small (5% of the average J‐manifold crystalline‐field splitting), however, as not to affect a first‐order crystal‐field analysis of the dominant portion of the spectrum. The crystal‐field parameters based on octahedral symmetry, B4 = 282 cm−1 and B6 = 74.7 cm−1, predict a splitting of crystal quantum states in good agreement with experiment.

Results to date indicate that plutonium can be absorbed at a reasonably rapid rate on any of several commercially available anion exchange resins from 7M nitric acid at 60 C. When the plutonium-loaded resin is then washed with 7M nitric acid, very high factors are obtained for separation of plutonium from uranium, fission products, and common ionic and nonionic impurities. The degree of separation depends on the extent of the washing cycle. Fission product separation factors as high as 3 x 10/sup 7/ have been obtained in two cycles of anion exchange. Urauium separation factors of comparable magnitude are possible with moderate volumes of wash solution. Product concentrations of greater than 50 grams of plutonium per liter are obtainable by eluting with dilute nitric acid at elevated temperature. Several resins show adequate resistance to chemical and radiation damage. Of the resins studied, Permutit SK shows the best combination of operating characteristics. Chemical and radiation stability and elution characteristics are outstanding. (auth)

MK-0366, a new derivative of nalidixic acid, was tested against 250 urinary pathogens including Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa. This new agent was more active than any of the other antibiotics tested, which included carbenicillin, ampicillin, cephalexin, tetracycline, trimethoprim, trimethoprim-sulfamethoxazole, and nalidixic acid. Gentamicin-resistant P. aeruginosa were highly sensitive to MK-0366, with a 90% minimal inhibitory concentration of 0.8 microgram/ml. Serratia strains were the most resistant organisms, with a 90% minimal inhibitory concentration of 3.1 micrograms/ml. These results suggest that clinical trials should be designed to investigate the clinical usefulness of this new drug in urinary infections.

Whole isolated rat glomeruli (WG) were incubated with bacterial collagenase to separate epithelial cells (EC) from the cores of glomerular tufts (GC), which consisted of mesangial and endothelial cells, as demonstrated by electron microscopy. Lysates of WG, EC, and GC and of renal tubules were prepared by hypo-osmotic shock and freeze-thawing. Activities of the following acidic lysosomal hydrolases were measured: acid phosphatase, beta-glucuronidase, cathepsin-D, non-specific esterase, and aryl sulfatases A and B. The glomerular cell preparations showed activities of all studied enzymes. GC had higher activities than EC, save for nonspecific esterase. Studies of the recovery of acid phosphatase and beta-glucuronidase revealed that approximately 2/3 of the hydrolase activities present in WG was still measureable after collagenase treatment and that the bulk of this was found in the GC lysates. These findings demonstrate that the rat glomerulus and its cell components have considerable biochemical activities of acidic hydrolytic enzymes. These appear to be most prominent in the combined mesangial and endothelial cells of the GC components.

The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1. The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined. Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation. All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion. In general, PGE was the predominant product. TPP and protein 1 also induced substantial secretion of thromboxane. Each cell-wall component was effective in stimulating mesangial IL-1 secretion. The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1. Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors. Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.