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Biomedical subjects

J L Ryan

Publications and source records attributed to J L Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1985

Ganglioside alterations in stimulated murine macrophages.

A two-dimensional thin-layer chromatographic technique has been used to separate and display gangliosides from murine peritoneal macrophages in different functional states. Resident macrophages have a relatively simple ganglioside pattern with about 15 resorcinol-positive spots. Gangliosides from resident cells contained mostly (90%) N-glycolylneuraminic acid. Thioglycolate-elicited and Corynebacterium parvum-activated macrophages have much more complex patterns with about 40 resorcinol-positive spots. Although ganglioside sialic acid content of stimulated macrophages was only slightly higher than that of resident cells, it consisted of nearly equal amounts of N-acetyl- and N-glycolylneuraminic acid. The shift in the ganglioside sialic acid type and the expression of different gangliosides in macrophages upon stimulation may help explain some of the differences in function and responsiveness noted in these macrophage populations.

Animals↗
PubMed1985

Effect of lipopolysaccharide on the stimulation of macrophage Fc-dependent phagocytosis by splenic B lymphocytes.

Macrophage phagocytic activity is regulated by a variety of products derived from activated lymphocytes. It has been reported that nonactivated splenic B and T lymphocytes enhance macrophage glucose metabolism. In addition, the enhancement of macrophage glucose metabolism was further increased by direct effects of bacterial lipopolysaccharide (LPS) on B, but not T, lymphocytes. In the present study, the effect of purified murine splenic B and T lymphocytes on Fc-dependent phagocytosis by thioglycollate-elicited peritoneal macrophages in the presence or absence of LPS has been investigated. Fc-dependent phagocytosis was assayed by measuring the ingestion of 51Cr-tagged sheep erythrocytes. After 3 or 4 days in culture, nonadherent spleen cells (NASC) and B and T lymphocytes from C3H/HeN (LPS-responder) mice produced 92 +/- 27%, 83 +/- 13%, and 147 +/- 33% increases in C3H/HeJ (LPS-hyporesponder) macrophage phagocytic activity, respectively. A similar effect was observed in Balb/c mice. Cell-free supernatant from NASC and B lymphocytes precultured for 2 or 4 days produced a 74 +/- 20% and 157 +/- 42% increase in phagocytosis respectively. At concentrations which have been previously shown to markedly enhance the ability of splenic B lymphocytes to stimulate macrophage glucose metabolism, Escherichia coli K235 LPS (10 micrograms/ml) did not alter the stimulatory effects of any of the splenic lymphocyte populations on macrophage Fc-dependent phagocytosis. These data suggest that B lymphocytes produce a soluble factor(s) which stimulates macrophage phagocytosis. In addition, LPS has different effects on the regulation of macrophage phagocytic activity and metabolism by B lymphocytes.

Animals↗
PubMed1985

Ganglioside modulation of lipopolysaccharide-initiated complement activation.

Highly purified preparations of mouse gangliosides have been demonstrated to bind to purified preparations of lipopolysaccharide (LPS). In some instances, the binding has been demonstrated to be dependent upon the presence of sialic acid in the ganglioside preparation. The binding of gangliosides to LPS from the deep rough Salmonella minnesota Re mutant has suggested that the interaction involves the lipid A-2-keto-3-deoxyoctulosanate region of the LPS macromolecule. The interaction between gangliosides and LPS has been demonstrated to result in an abrogation of lipid A dependent activation of the classical pathway of serum complement by Re LPS. Surprisingly, however, the presence of sialic acid containing glycolipids has been shown to enhance significantly the capacity of LPS to initiate activation of the alternative pathway of complement. These data suggest that sialic acid can enhance as well as inhibit the formation of a stable alternative-pathway C3 convertase.

Animals↗
PubMed1985

Further studies on the influence of chemical form and dose on absorptions of Np, Pu, Am and Cm from the gastrointestinal tracts of adult and neonatal rodents.

Absorption of isotopes of the actinide elements Np, Pu, Am and Cm from various organic media and/or in combination with plant or animal ligands or tissue is compared with their absorption from an inorganic nitrate medium. Gastrointestinal (GI) transport of 238Pu, 239Pu, 241Am and 244Cm at high concentrations from citrate medium by adult rats and/or mice was higher than from nitric acid medium. Neptunium-237 absorption, however, was not increased by citrate; probably because its oxidation state was reduced from 237Np(V) to 237Np(IV) by the medium and by the GI content. Increasing the mass of the 237Np dose resulted in increased absorption. Neither incorporation of 238Pu in rat liver nor retention of 238Pu oxide in rat lungs enhanced absorption when those Pu-containing tissues were administered intragastrically to either adult or neonatal rats. Ranking of GI absorption of the various forms of Pu gavaged in these studies suggests that transport is in the order: Pu citrate greater than Pu phytate greater than biologically incorporated Pu greater than Pu nitrate.

Actinoid Series Elements↗
PubMed1985

Does bacteremia occur during flexible sigmoidoscopy?

Up to 10% of patients may have bacteremia after rigid sigmoidoscopy. The aim of our study was to determine the frequency of bacteremia accompanying flexible sigmoidoscopy. Blood samples for aerobic and anaerobic cultures were obtained before, during, and after flexible sigmoidoscopy in 100 patients who were examined a mean distance of 49.5 cm, range 15-60 cm, after a bowel preparation of two Fleet enemas. In one patient, a transient bacteremia with Streptococcus intermedius was documented and was attended by no associated clinical manifestations. This organism has been previously isolated from patients with endocarditis, peritonitis, emphysema, and hepatic and appendiceal abscesses. There was no association in our study with bacteremia and such factors as length of bowel examined and duration of procedure, the presence of bowel pathology, performance of endoscopic biopsies, liver disease, and portal hypertension or poor bowel preparation. We conclude that the extremely low incidence of significant bacteremia with flexible sigmoidoscopy may be related to the smaller diameter of the instrument and provides further support for the routine use of flexible rather than rigid sigmoidoscopy.

Adult↗
PubMed1984

Optimal therapy for enterococcal endocarditis.

Enterococcal endocarditis accounts for an increasing proportion of cases of endocarditis in recent years. The combination of a penicillin and an aminoglycoside has become an accepted standard of treatment for this disease. However, the optimal choice of antibiotics, duration of therapy, and timing of surgical intervention remain controversial. This study reviews the presentation, clinical course, treatment, and outcome in 37 patients with 42 separate episodes of enterococcal endocarditis at four Yale University hospitals. Patients treated with aminoglycosides and penicillins or vancomycin had significantly better outcomes than those who did not receive aminoglycosides. However, the duration of aminoglycoside therapy (more than four versus less than four weeks) did not appear to affect outcome significantly. These results suggest that excellent cure rates may be achieved after treatment for less than four weeks with an aminoglycoside in combination with penicillin or vancomycin, thus potentially avoiding significant renal and vestibular toxicity.

Aminoglycosides↗
PubMed1984

Effect of intravenous recombinant alpha-2 interferon on monocyte Fc-dependent phagocytosis in patients with malignant melanoma.

Recombinant alpha interferons (IFN-alpha) have diverse effects on the immune response. Alpha IFNs have been shown to increase the number of monocyte Fc receptors and Fc dependent phagocytosis in vitro. Therefore, we prospectively evaluated Fc-dependent phagocytic activity in a group of 14 patients with Stage III melanoma receiving from 10 to 100 X 10(6) u of recombinant DNA-produced alpha-2 interferon (IFN-alpha 2) five days a week for four weeks. Monocyte Fc-dependent phagocytosis (FcDP) was assayed by measuring the ingestion of 51Cr-labeled, IgG-coated sheep erythrocytes before, and on Days 2, 5, and 19 of IFN therapy. Each patient was simultaneously compared with the same unmatched normal controls during the assay period. Monocyte FcDP was unchanged in 8/14 patients on each of the three sampling days. Increases in FcDP occurred in 4/14 patients on Day 2 and only 1/14 on Day 19. Recombinant DNA-produced IFN-alpha 2 did not persistently augment monocyte FcDP irrespective of the dose administered. Moreover, there may be untoward effects on monocyte FcDP in vivo from intravenous administration of high dose IFN-alpha 2 since a distinct, but statistically insignificant (p = 0.06) trend of inhibition of FcDP by Day 19 of therapy was observed. Monocyte FcDP activity of normal controls fluctuated from day to day. The intrinsic variability in monocyte FcDP as assessed by this technique may conceal an effect(s) of IFN preparations in vivo. Additional studies are needed to further define the effects of purified IFN preparations on monocyte and tissue-derived macrophage effector functions.

Cloning, Molecular↗
PubMed1984

Acetylated diamines inhibit endotoxin-induced lymphocyte activation.

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.

Acetamides↗
PubMed1984

Enhancement of macrophage immune and nonimmune receptor-mediated phagocytosis by a low molecular weight soluble factor from resident thymocytes.

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).

Animals↗
PubMed1984

Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

Aging↗
PubMed1983

Pneumococcal pneumonia in hospitalized patients. Clinical and radiological presentations.

The clinical and radiological features of pneumococcal pneumonia were studied in 94 hospitalized patients. Fifty-seven (61%) had a bronchopneumonic pattern on roentgenogram, and 37 (39%), a lobar pattern. Eighty-two (87%) of the patients in both roentgenographic classifications had one or more underlying disease states. There was no difference in the frequency of heart disease, diabetes, chronic pulmonary disease, or malignancy between the two categories. Sputum Gram's stains were also similar in both patterns. Twenty (54%) of the 37 patients with the lobar pattern were bacteremic compared with only five (9%) of the 57 patients with the bronchopneumonic pattern; all five patients with bronchopneumonia and bacteremia had an associated malignancy. Although a lobar pattern is usually emphasized in the diagnosis of pneumococcal pneumonia, this study showed that the majority of patients hospitalized with pneumococcal pneumonia had a roentgenographic bronchopneumonic pattern rather than the classic lobar pattern. Thus, patients with the bronchopneumonic pneumococcal pneumonia pattern may be underdiagnosed. The implications are important both for treatment and for epidemiologic data used in the selection of pneumococcal types for prophylactic vaccines.

Aged↗
PubMed1983

Neutral proteinase activity produced in vitro by cells of the glomerular mesangium.

Cells derived from isolated glomerular tufts of rats were studied in primary tissue culture after the removal of epithelial cells by collagenase treatment. The cultured cells, fusiform or stellate in shape, grew readily over a 12-day period. Immunofluorescence staining was positive for myosin and fibronectin, while negative for Factor VIII, suggesting that the outgrowing cells were derived from the glomerular mesangium. In serum-free culture, these cells produced neutral proteinase activity that occurred as a latent trypsin-activable form (apparent molecular weight range, 78,000 to 100,000 daltons) and in an active form (44,000 to 58,000 daltons). Neutral proteinase activity was inhibited by EDTA and by cysteine, and exhibited a pH optimum of 7.2 to 7.8, characteristic of an extracellularly active metalloendopeptidase. The culture supernate which contained the neutral proteinase activity was capable of degrading purified rat glomerular basement membrane. The release of hydroxyproline-containing fragments from the basement membrane indicated that degradation of the type IV collagen component of the basement membrane was occurring. These findings suggest that the neutral proteinase activity generated by mesangium-derived cells may play a role in the physiologic turnover of glomerular structural proteins in vivo.

Animals↗
PubMed1983

Functional heterogeneity of the Lyb-5- B cell subpopulation: mutant xid B cells and normal Lyb-5- B cells differ in their responsiveness to phenol-extracted lipopolysaccharide.

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.

Animals↗
PubMed1983

Enhancement of macrophage Fc-dependent phagocytosis by resident thymocytes: effect of a unique heat-stable lymphokine.

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.

Animals↗
PubMed1983

A thymocyte-activating factor derived from glomerular mesangial cells.

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.

Animals↗