Acute lung injury, acute respiratory distress syndrome and inhalation injury: an overview.

Acute Lung Injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS) are severe respiratory diseases that have a very poor prognosis and have numerous causes. Despite a great deal of research and investigation since the initial description of ARDS 30 years ago many questions about the pathogenesis, treatment and outcome of the disease remain unanswered. Although there is evidence to suggest that outcome of ALI and ARDS is improving, the reasons why are unknown and there is not yet a well developed treatment for these diseases.

Aerosol deposition modeling using ACSL.

An aerosol deposition model has been written for inclusion into physiologically based pharmacokinetic (PBPK) models, allowing PBPK model based risk assessments to be performed for aerosolized materials. Previously, PBPK models could only treat inhaled gases and vapors. The deposition model employs a semi-empirical equation to describe extrathoracic deposition and employs data concerning the geometry of the thoracic conducting airways as well as that of the gas exchange regions of the lung to compute the deposited aerosol mass based on aerosol diffusion, sedimentation, and impaction.

Breathing zone particle size and lead concentration from sanding operations to remove lead based paints.

The relationship between lead concentration in the dry film of lead based paints applied to steel bulkheads aboard ship, the lead concentration found in the air when the paint is removed by mechanical means, and blood lead concentrations of workers involved in lead based paint removal has not been well characterized. Intuitively a direct relationship must exist but confounding factors confuse the issue. Simultaneous sampling procedures from the same paint removal operation may differ by several orders of magnitude.

Evidence for distinct intracellular signaling pathways in CD34+ progenitor to dendritic cell differentiation from a human cell line model.

Intracellular signals that mediate differentiation of pluripotent hemopoietic progenitors to dendritic cells (DC) are largely undefined. We have previously shown that protein kinase C (PKC) activation (with phorbol ester (PMA) alone) specifically induces differentiation of primary human CD34+ hemopoietic progenitor cells (HPC) to mature DC. We now find that cytokine-driven (granulocyte-macrophage CSF and TNF-alpha) CD34+ HPC-->DC differentiation is preferentially blocked by inhibitors of PKC activation.

Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed in Panama.

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo.

A comparative study of the cell cycle status and primitive cell adhesion molecule profile of human CD34+ cells cultured in stroma-free versus porcine microvascular endothelial cell cultures.

Porcine microvascular endothelial cells (PMVECs) plus cytokines support a rapid proliferation and expansion of human CD34+CD38- cells that are capable of multilineage engraftment within the bone marrow of a secondary host. CD34+CD38- cells contain the self-renewing, long-term culture-initiating cells (LTC-IC) that are ideal targets for retroviral gene transfer experiments. Previous experiments attempting retroviral infection of CD34+CD38- cells have failed partly because these cells do not enter cell cycle in response to cytokine combinations.

Exotic virus infections of military significance. Hemorrhagic fever viruses and pox virus infections.

Military personnel are frequently deployed to distant locations around the world under conditions of great stress, which involve potential exposure to hazardous viruses that are not commonly seen in the developed world. This article will provide an overview of two clinical presentations of viral infections of potential military significance: hemorrhagic fever and poxvirus infections. The three viral hemorrhagic fever viruses described--dengue, hemorrhagic fever with renal syndrome, and Congo-Crimean hemorrhagic fever--represent the diversity of potential hemorrhagic fever viruses that military forces may be exposed.

The establishment of good laboratory practices at the Naval Medical Research Institute Toxicology Detachment.

A quality-management program (QMP) has been launched at the Naval Medical Research Institute Toxicology Detachment to support the planning, assessment, interpreting, and reporting of toxicology study data. The QMP conforms to the intent of the Good Laboratory Practice established by the Food and Drug Administration and the Environmental Protection Agency for regulatory compliance. The biomedical data necessary to characterize the toxicity of materials of interest to the Navy are used to formulate occupational and environmental health-hazard evaluations and risk assessments, including appropriate exposure limits for personnel for Navy-specific circumstances of exposure.

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure.

Detection of Apoptosis in HIV-Infected Ceil Populations using TUNEL.

Cells within an organism undergo two common forms of cell death. Sudden injury resulting from physical or chemical insult leads to a form of cell death called necrosis. A more subtle programmed form of cell death is termed apoptosis.

Telomeric Terminal Restriction Fragment (TRF).

Telomeres are protein-DNA structures at the ends of all eukaryotic chromosomes that are maintained by a unique ribonucleoprotein known as telomerase. This highly specialized RNA-dependent DNA polymerase provides a critical solution to the end-replication problem by adding TTAGGG repeats to 3' ends of human chromosomes (1-3). Telomere regulation is both cell cycle and developmentally-regulated, and its control is likely to be complex (4,5).

CTLA4 (CD152) modulates the Th subset response and alters the course of experimental Leishmania major infection.

Since both the nature and the amplitude of an antigen-specific T cell response are dependent on co-stimulatory signals, we have investigated the role of CD28/CD152-mediated T cell co-stimulation in the regulation of experimental cutaneous leishmaniasis. CD28-deficient mice and their wild-type littermates are equally susceptible to Leishmania major infection. Whole anti-CD152 antibody significantly exacerbates the disease while anti-CD152 Fab ameliorates the disease in genetically susceptible BALB/c mice but not in C57BL/6, a resistant strain.

In vitro expression and in vivo immunogenicity of Plasmodium falciparum pre-erythrocytic stage DNA vaccines.

DNA vaccine plasmids were constructed that encoded four pre-erythrocytic antigens from the human malaria parasite Plasmodium falciparum: circumsporozoite protein (PfCSP); sporozoite surface protein 2 (PfSSP2); carboxyl terminus of liver stage antigen 1 (PfLSA-1 c-term); and, exported protein 1 (PfExp-1). Antigen expression was evaluated in vitro by immunoblot analysis of tissue culture cells following transient transfection with each plasmid. Clearly detectable levels of expression depended upon, or were markedly enhanced by, fusion of the antigen encoding sequences in-frame with the initiation complex and peptide leader sequence of human tissue plasminogen activator protein.

Calculation of exposure chamber leak rate with thermal correction: a measure of chamber integrity.

A method for assessing inhalation exposure chamber integrity by calculation of leak rate was modified to account for temporal changes of temperature in the chamber. In a well-sealed chamber, accounting for thermal effect brought observed leak rates into better agreement with predicted values. Mean estimates of chamber leak rate without thermal correction ranged from 2.

Large-scale production of CD4+ T cells from HIV-1-infected donors after CD3/CD28 costimulation.

We describe a procedure for large-scale enrichment, growth, and harvesting CD4+ T cells. This method may be effective for HIV-1 immunotherapy, as the mode of stimulation, with anti-CD3 plus anti-CD28 coated beads (CD3/CD28 beads) induces a potent antiviral effect. PBMC were obtained by density gradient centrifugation of an apheresis product.

Tissue distribution, metabolism, and clearance of the convulsant trimethylolpropane phosphate in rats.

The distribution, metabolism, and clearance of trimethylolpropane phosphate (TMPP), a potent, bicyclophosphate, gamma-aminobutyric acid-ergic convulsant, were studied in male Fischer-344 rats. Intraperitoneal administration of TMPP was compared with oral gavage with respect to rates of absorption, distribution, and clearance. Distribution of TMPP to major body tissues was evaluated for the first 24 hr after administration or, in the case of regional brain distribution, immediately after the first TMPP-induced clinical seizure.

Complete nucleotide sequence analysis of a Western Pacific dengue-1 virus strain.

We have determined the complete nucleotide sequence and the deduced amino acid polypeptide sequence of the genome of a dengue-1 (DEN-1) virus strain isolated from a patient on Nauru in the Western Pacific in 1974 (West Pac 74). The complete genome is 10,735 nucleotides in length and contains a single long open reading frame of 10,176 nucleotides encoding a polyprotein of 3392 amino acids. When compared to DEN-1 Singapore S275/90, the nucleotide and amino acid sequence homology are 94% and 97.

Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine.

CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naïve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent CTLs.

Relationship between T-wave amplitude and oxygen pulse in guinea pigs in hyperbaric helium and hydrogen.

Diving is known to induce a change in the amplitude of the T wave (ATw) of electrocardiograms, but it is unknown whether this is linked to a change in cardiovascular performance. We analyzed ATw in guinea pigs at 10-60 atm and 25-36 degreesC, breathing 2% O2 in either helium (heliox; n = 10) or hydrogen (hydrox; n = 9) for 1 h at each pressure. Core temperature and electrocardiograms were detected by using implanted radiotelemeters.

Immune response against the exp-1 protein of Plasmodium falciparum results in antibodies that cross-react with human T-cell lymphotropic virus type 1 proteins.

To examine the role of the Plasmodium falciparum Exp-1 blood-stage protein in producing antibodies that cross-react with human T-cell lymphotropic virus type I (HTLV-I) proteins, we studied sera from Indonesian volunteers who seroconverted to malaria after transmigrating to an area where malaria is hyperendemic. Samples from Philippine volunteers, that were used in a prior study that examined malaria antibodies that cross-react with HTLV-I proteins, were also used. Eighty-three percent of the Indonesian transmigrants developed antibodies against the malaria Exp-1 protein by 6 months postmigration.

Decompression sickness risk in rats by microbial removal of dissolved gas.

We present a method for reducing the risk of decompression sickness (DCS) in rats exposed to high pressures of H2. Suspensions of the human colonic microbe Methanobrevibacter smithii were introduced via a colonic cannula into the large intestines of the rats. While the rats breathed H2 in a hyperbaric chamber, the microbe metabolized some of the H2 diffusing into the intestine, converting H2 and CO2 to methane and water.

A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine.

Using the murine parasite Plasmodium yoelii (Py) as a model for malaria vaccine development, we have previously shown that a DNA plasmid encoding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP1012 with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) increases protection against malaria, and we have characterized in detail the increased immune responses due to GM-CSF. PyCSP1012 plasmid alone protected 28% of mice, and protection increased to 58% when GM-CSF was added (p < 0.

Geographic distribution and clinical description of leishmaniasis cases in Peru.

Studies were conducted from 1986 through 1993 to further define the geographic distribution and relative importance of different species of Leishmania as a cause of leishmaniasis in Peru. Patients with a clinical diagnosis of cutaneous and/or mucosal or diffuse cutaneous leishmaniasis were enrolled at the Naval Medical Research Institute Detachment (NAMRID) Laboratory in Lima, the Tropical Disease Clinic at San Marcos University Daniel A. Carrión, the Central Military Hospital, and a Ministry of Health hospital in Cusco, Peru.

Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids.

CD8(+) T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8(+) T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8(+) T-cell responses against multiple P.