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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 451 records · Page 25Linked to original sources
PubMed1988

Immunosuppression in the surgical patient.

A review of both the healthy and altered immune response as it relates to the surgical patient is presented. An increasing number of immunosuppressive states have been defined in the surgical patient including trauma, burns, sepsis, malnutrition, cancer, and, more recently, acquired immunodeficiency syndrome (AIDS).Investigations of the healthy and altered immune response have led to the development of immunopharmacology, which involves the study of pharmacologic agents that modify host immune response to achieve desired therapeutic goals. Endogenous and exogenous immunomodulators are described that affect uniquely the host immune response as well as their therapeutic implications.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effect of enhanced macrophage function on early wound healing.

Although the macrophage is important to wound healing, research has focused on its relationship to fibroblast and collagen synthesis. This study was designed to assess effects of enhanced macrophage function on early wound healing, before established collagen synthesis. Sprague-Dawley rats had dorsal incisions after one of three treatment regimens: (1) saline solution, 0.5 ml administered intravenously, (2) intravenous glucan, a macrophage stimulant, 20 mg; (3) topical glucan, 20 mg. Intravenous therapy was administered 24 hours before and after incision. Breaking strength was significantly increased (p less than 0.01) by both intravenous glucan (49.8 +/- 5.5 gm) and topical glucan (59.7 +/- 5.6 gm) on the fourth day after incision, compared with controls (22.0 +/- 2.6 gm). Similar results occurred on the seventh day after incision. Although formalin fixation significantly enhanced breaking strength in fresh control wounds (22.0 +/- 2.6 vs 39.5 +/- 2.2 gm), no increase occurred in wounds treated with intravenous glucan (49.8 +/- 5.0 vs 55.3 +/- 6.4 gm), indicating maximal cross-linking of collagen. Collagen synthesis, reflected by tritiated proline uptake, was no different in control versus glucan groups. Supernatants from control or glucan-activated macrophages were injected intraperitoneally or applied topically in the rat model. Activated supernatant, both intraperitoneal and topical, resulted in increased breaking strength on the fourth day after incision. Formalin fixation did not increase breaking strength in the activated supernatant groups. We conclude that enhanced macrophage function increases early wound breaking strength. This effect appears unrelated to collagen synthesis but may be related to increased cross-linking of collagen. Similar effects are seen with activated macrophage secretory products administered intraperitoneally or topically.

Administration, Topical↗
PubMed1987

Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia?

The Ehrlichia are tick-borne rickettsial organisms that cause disease in animals throughout the world but that have been previously recognized as human pathogens only in Asia. We have identified six patients with serological evidence of recent infection with an Ehrlichia: a fourfold or greater rise or fall in titer to Ehrlichia canis. All of the patients reported recent tick bites. Rigors, myalgia, headache, nausea, and anorexia were each reported by five patients. Fever was present in all patients and was accompanied by relative bradycardia and leukopenia in five patients, thrombocytopenia and abnormal liver function test results in four, and anemia in three. Five of the six patients were treated with tetracycline hydrochloride, and all recovered. Infection with Ehrlichia should be considered in patients with unexplained febrile illnesses after tick exposure.

Adult↗
PubMed1987

Experimental histoplasmosis in the beige mouse.

Mice carrying the beige mutation (bg/bg) on a C57Bl/6 background were challenged with Histoplasma capsulatum. bg/bg mice had higher mortality and higher lung tissue fungal counts in their lungs than either bg/+ or C57Bl/6 mice challenged with equal inocula. Immunologic studies showed that bg/bg mice developed normal delayed-type hypersensitivity (DTH) reactions to histoplasmin, but had deficient NK cell cytotoxic activity against YAC-1 target cells. Studies of macrophage killing of H. capsulatum in vitro showed that T lymphocytes of either bg/+ or bg/bg mice were able to activate fungal killing by bg/+ but not by bg/bg macrophages. These studies, while not excluding a role for the NK cell, suggest that macrophage dysfunction may be critical in the greater susceptibility of the bg/bg mouse and, by extension, that macrophage function is of major importance in host defense against H. capsulatum.

Animals↗
PubMed1987

Protective effect of glucan-enhanced macrophage function in experimental pancreatitis.

In an effort to assess the impact of enhanced macrophage function in acute pancreatitis, mice were subjected to a choline-deficient diet supplemented by ethionine to induce necrotizing pancreatitis. Treatment with the macrophage stimulant glucan resulted in improved survival rates (58 percent versus 14 percent) and maintenance of pancreatic architecture. Glucan treatment also resulted in decreased plasma and peritoneal trypsin activity, as well as increased trypsin-binding activity in the blood and peritoneal cavity. Plasma interleukin-1, as well as macrophage production of interleukin-1, were increased in the glucan-treated mice, which indicated enhanced macrophage function. These composite findings suggest that by enhancing diverse aspects of reticuloendothelial function, clinical use of immunomodulators may have significant impact on the pathogenesis of acute pancreatitis.

Acute Disease↗
PubMed1987

Autocytotoxic and autosuppressor T-cell lines generated from autologous lymphocyte cultures.

Limiting dilution analyses have demonstrated both the generation and suppression of autocytotoxic cells following in vitro stimulation with autologous peripheral blood mononuclear leukocytes (PBL). Therefore, in order to isolate and characterize the autocytotoxic lymphocytes, interleukin 2-dependent cell lines were derived from autologous mixed lymphocyte microcultures. The cell lines were screened for cytolytic activity against autologous phytohemagglutinin-activated lymphoblasts, autologous and allogeneic B-lymphoblastoid cell lines (B-LCL), and the natural killer target K562. Of 189 cell lines analyzed, 26 demonstrated cytotoxicity against autologous target cells. Cell surface phenotyping of all cell lines indicated that they were of T lymphocyte lineage. Two autocytotoxic T-cell clones were subsequently derived in similar fashion. Cell lines were also screened for autoregulatory activity. Two cells lines were identified that inhibited the generation of autocytotoxicity. Neither of the autoregulatory lines was capable of directly lysing an autocytotoxic line, suggesting that these autosuppressor cells exert their inhibitory effect by a mechanism other than direct lysis of the autocytotoxic effector cell. These findings indicate that through the application of limiting dilution analysis and in vitro cell culture techniques, autocytotoxic and autosuppressor lymphocyte populations can be isolated and utilized to analyze the cellular interactions involved in maintaining self-tolerance.

Autolysis↗
PubMed1987

Small area analysis: a review and analysis of the North American literature.

Variations in health service use rates by geographic area have long interested researchers and policymakers. Typically, investigators comparing population-based health care utilization rates among geographic areas have demonstrated substantial variations in use among seemingly similar communities. One method of investigation is "small area analysis." Numerous areas in North America have been studied extensively using this technique. This research has attempted to document the amount of variation found in health care use rates among areas; determine whether or not there is a pattern to such use in high- versus low-use areas; and identify the variables that are associated with the variation and explain a portion of the variation. Beyond this, many researchers have attempted to ascertain whether such variables are associated with characteristics of the population, whether they reflect differences in access and need, or whether a substantial portion of the variation is associated with differences in the medical care system itself. This review discusses the methods used to define the areas, the dependent variables that have been studied and the patterns found within them, the independent variables that have been tested, the statistical methods and analysis procedures used, the results of each study, and the policy recommendations emanating from the research. More importantly, based on what has been learned, the paper provides researchers in small area analysis with a set of recommendations for both analyzing and reporting results. These recommendations are designed to facilitate the development of a common research methodology, increase the comparability across studies, and enhance the use of this technique in the health policy formulation process.

Bibliographies as Topic↗
PubMed1987

Cooperative phenomena in the perception of motion direction.

A percept of global coherent motion can result from the combination of many different localized motion vectors. We report here evidence of hysteresis in the perception of this global motion, obtained with random-dot cinematograms. The hysteresis characteristics are relatively robust with respect to changes in dot density, display area, and location. Changing the directional content of the stimulus, however, did alter the hysteresis profile in a manner consistent with a model incorporating cooperative interactions among direction-selective motion mechanisms. Our results lend further support to a cooperative interpretation of motion results lend further support to a cooperative interpretation of motion perception in random-dot cinematograms.

Humans↗
PubMed1987

Genetic assembly and selective toxicity of diphtheria-toxin-related polypeptide hormone fusion proteins.

The reports of Miyanohara et al. (1986) and Murphy et al. (1986) were the first to describe the genetic construction, expression, and receptor-specific selective toxicity of a chimaeric toxin. In the present report, we have extended these earlier observations and have shown that the fusion of a modified gene encoding IL-2 to a truncated diphtheria toxin gene also results in the expression of a biologically active chimaeric IL-2 toxin. In both instances we have used receptor-binding-domain substitution and have genetically coupled those portions of the diphtheria toxin structural gene that encode the ADP-ribosyl transferase activity of fragment A and lipid-associating domains of fragment B to modified genes which encode either the polypeptide hormone alpha-MSH or the T-cell growth factor IL-2. The chimaeric toxins expressed from these gene fusions have been shown to be selectively targeted to those eukaryotic cells that carry specific surface receptors for the ligand compounds of the hybrid. For example, in the case of the IL-2 toxin, it is clear that the selective action of this hybrid protein is based upon both its diphtheria-toxin and IL-2-related components. Following binding to the IL-2R on activated and/or malignant T-cell, IL-2 toxin is internalized by receptor-mediated endocytosis. Upon acidification of the endosome, diphtheria toxin fragment B portions of the chimaeric toxin facilitate the delivery of fragment A to the cytosol where it catalyses the ADP ribosylation of EF-2. The assembly of chimaeric toxins at the level of the gene offers several advantages over chemical linkage. Since chemical linkage of the toxophore and ligand components of the conjugate toxins requires activation of the epsilon-amino moiety of lysine residues with reagents that will allow for subsequent disulphide linkage, the precise site of coupling is generally not known. In addition, there has been considerable concern over the lability of the disulphide bond between the toxophore and ligand components in vivo due to the action of disulphide reductases. The assembly of chimaeric toxins at the level of the gene allows for precise linkage of the toxophore and ligand components. Since the linkage between the toxophore and ligand is a peptide bond, the chimaeric toxin should be stable in vivo. In addition, the genetic construction of chimaeric toxins also allows for further protein engineering through site-directed mutagenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1987

Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis.

To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis. ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment. All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally. Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%). Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups. Combined therapy significantly reduced E. coli bacteremia at 8 hours after inoculation, when compared with the other three groups. Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay. Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils. Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E. coli peritonitis. This combined therapy enhanced macrophage secretory activity and bone marrow proliferation. Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.

Animals↗
PubMed1987

Modulation of Friend virus infectivity in vivo by administration of purified preparations of human lactoferrin and recombinant murine interleukin-3 to mice.

Purified iron-saturated human milk lactoferrin (LF) and purified recombinant murine interleukin-3 (IL-3) were assessed in vivo for their effects on replication of spleen focus forming viruses (SFFV) in spleens of DBA/2 mice injected with the polycythemia-inducing strain of the Friend virus complex. LF and IL-3, inoculated 2 hr prior to the administration of the polycythemia-inducing strain of the Friend virus complex, respectively decreased and increased the replication of SFFV in mice as assessed by the spleen focus forming unit assay in primary and secondary DBA/2 mice. Since virus infectivity is associated with the DNA synthetic phase of the cell cycle and it has been shown elsewhere that LF decreases and IL-3 increases the percent of hematopoietic progenitor cells in S-phase in vivo, the results suggest that the opposing actions of LF and IL-3 on replication of SFFV may reflect the actions of these molecules on cycling of the target cells for SFFV.

Animals↗