Catecholaminergic, cholinergic and peptidergic innervation of gut-associated lymphoid tissue in porcine jejunum and ileum.

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. Using immunohistochemical techniques, we tested the hypothesis that gut-associated lymphoid tissue in the porcine small intestine might receive catecholaminergic, cholinergic and peptidergic innervation. Antibodies against protein gene product (PGP) 9.

Potentiation of anaphylaxis in guinea pig ileal mucosa by a selective delta-opioid receptor agonist.

Immediate hypersensitivity reactions in the intestinal mucosa evoke active chloride secretion which enhances the elimination of luminal antigens. The prosecretory actions of histamine and other soluble mediators of anaphylaxis are mediated by submucosal neurons, as are the antisecretory actions of opioid antidiarrheal medications. We tested the hypothesis that the selective delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) alters anaphylaxis-associated ileal anion secretion in vitro.

Characterization of monoclonal antibodies to an immunodominant protein of the etiologic agent of human granulocytic ehrlichiosis.

Immunodominant proteins in the range of 42-45 kD are important for the serodiagnosis of human granulocytic ehrlichiosis (HGE). Antigens from human isolates of the etiologic agent of HGE cultivated in HL-60 cells were used to immunize BALB/c mice and generate a panel of hybridomas secreting monoclonal antibodies. Using an enzyme immunoassay, an immunofluorescent assay (IFA), and Western blotting, we showed that culture supernatants and ascites of these hybridomas were reactive with human isolates of the etiologic agent of HGE, Ehrlichia equi and E.

Right heart catheterization in acute lung injury: an observational study.

Right heart catheterization (RHC) is commonly used in the diagnosis and management of acute lung injury (ALI). However, controversy exists regarding RHC. We examined RHC use during the first 3 d of ALI in an observational study of 135 patients defined by American-European Consensus Conference criteria.

Inhibition of K-ras-transformed rodent and human cancer cell growth via induction of apoptosis by irreversible inhibitors of Ras endoprotease.

Proteolytic removal of the carboxyl terminal tripeptide of Ras oncoproteins is important in the Ras function. Two chloromethyl ketones, BFCCMK and UM96001, designed to be the Ras C-terminal sequence-specific endoprotease inhibitors, at low micromolar concentrations (5.0 microM), potently inhibit the growth of ras-transformed rodent and human cancer cells, whereas untransformed NIH/3T3 cells are not affected under the same conditions.

Delta-opioid receptor mRNA expression and immunohistochemical localization in porcine ileum.

Opiates have potent antidiarrheal actions that are mediated in part by delta-opioid receptors (DOR). We examined DOR localization within subregions of porcine ileum, a tissue analogous to human small bowel. A partial cDNA sequence for porcine DOR was obtained after reverse transcription-polymerase chain reaction cloning of forebrain RNA; it encoded the end of transmembrane domain 1 through the beginning of transmembrane domain 7 and exhibited 93% nucleotide identity with human DOR.

Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human isolates.

Human granulocytic ehrlichiosis (HGE) is an emerging infection caused by an Ehrlichia species closely related to Ehrlichia equi and Ehrlichia phagocytophila. Recent advances in the isolation and cultivation of this organism have allowed us to develop an immunofluorescence assay (IFA), enzyme immunoassay (EIA), and Western immunoblotting (WB) using HL-60 cell culture-derived human isolates. Antibody was detected in sera from culture-confirmed HGE patients by IFA and EIA, and these samples were reactive when analyzed by immunoblot analysis.

Protease inhibitors for the treatment of human immunodeficiency virus infection.

The pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration of protease inhibitors are reviewed. Protease inhibitors are a novel class of drugs used for the treatment of human immunodeficiency virus (HIV) infection. Saquinavir, ritonavir, indinavir, and nelfinavir have been approved in the United States; several other agents are under development.

Prognostic significance of the CD10+CD19+CD34+ B-progenitor immunophenotype in children with acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Leukemic cells from most patients with B-lineage acute lymphoblastic leukemia (ALL) appear to originate from normal B-lymphocyte precursors. The earliest B-cell progenitors coexpress the antigens CD10, CD19, or CD34 on their cell surfaces. In a large cohort of 2028 children with ALL, we compared treatment outcomes of a subset of B-lineage ALL patients with CD10+CD19+CD34+ immature B-progenitor leukemia (BPL) to the treatment outcomes of the remaining CD19+ B-lineage ALL patients.

Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia.

We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg.

Pharmacokinetics of hyperimmune anti-human immunodeficiency virus immunoglobulin in persons with AIDS.

Hyperimmune anti-human immunodeficiency virus immunoglobulin (HIVIG) is an intravenous immunoglobulin prepared from HIV-infected asymptomatic donors with a CD4 cell count greater than 400 cells/microl and a high titer of antibody to HIV-1 p24 protein. Twelve persons with AIDS received four doses of HMG (two at 50 mg/kg of body weight and then two at 200 mg/kg) every 28 days. Pharmacokinetics were evaluated by measurement of anti-p24 antibody.

Creating a healthy work environment in the midst of organizational change and transition.

In the midst of organizational change and transition, the need for a healthy work environment is greater than ever. Leaders may be in a position of leading staff on a journey they would rather not be on. Although there may not be a choice of destination, there are many decisions to be made along the way that will impact the health and quality of the journey.

A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor.

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2.

Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukemias.

Contemporary therapies for acute myeloid leukemia (AML) commonly fail to cure patients because of the emergence of drug resistance. Drug resistance in AML is multifactorial but can be associated with the overexpression of transmembrane transporter molecules, including P-glycoprotein (Pgp) or the multidrug resistance-associated protein (MRP), or associated with inactivation of the p53 tumor suppressor gene, as well as overexpression of the anti-apoptotic protein bcl-2. We are investigating if novel recombinant biotherapeutics can circumvent these resistance mechanisms to effectively treat refractory AML.

Pharmacokinetic features, immunogenicity, and toxicity of B43(anti-CD19)-pokeweed antiviral protein immunotoxin in cynomolgus monkeys.

We studied the pharmacokinetic features, immunogenicity, and toxicity of B43-pokeweed antiviral protein (PAP) immunotoxin in 13 cynomolgus monkeys. The disposition of B43-PAP in two monkeys, when administered as a single i.v.

Differential effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the radiation sensitivity of normal versus leukemic bone marrow progenitor cell populations.

We examined the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF), interleukin 3 (rhIL-3) and interleukin 6 (rhIL-6) on the radiation sensitivity of normal and leukemic bone marrow progenitor cell populations. Conditioning of leukemic progenitor cells (LPC) from acute lymphoblastic leukemia (ALL) patients with rhG-CSF enhanced their radiation sensitivity, whereas conditioning with rhIL-3 or rhIL-6 had the opposite effect. In contrast to its effects on LPC derived from ALL patients, rhG-CSF reduced the radiation sensitivity of normal myeloid progenitor cells as well as LPC from acute myeloblastic leukemia (AML) patients.

Relationship between follicular nerve supply and alopecia.

The emergence of new technologies such as the combination of immunohistochemical techniques with laser scanning confocal microscopy allows one to observe and project the three-dimensional perifollicular innervation in tissue sections measuring up to 200 microns. This technology opens the door to making new discoveries about the innervation of the hair follicle. As new information is generated about the cutaneous sensory nervous system, neuropeptide expression, and the modulation of inflammatory and proliferative processes by the nervous system in the skin, it is likely this knowledge will be applied to enhance our understanding of the biology of the hair follicle in both the normal and diseased state.