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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 397 records · Page 22Linked to original sources
PubMed1978

First-pass effect of norethindrone in rabbits and rats.

The influence of the route of administration on the pharmacokinetics of the synthetic progestogen norethindrone was studied in the rabbit and rat. In the rabbit, the area under the curve (AUC) after oral administration was 54% of that after i.v. administration. In the rat, the AUC after administration into the hepatic portal vein was 32% of AUCi.v.; after oral administration the AUCoral was 13.7% of AUCi.v. and 57.6% of AUCportal. Therefore, in both the rabbit and rat norethindrone is subject to a first-pass effect. Using the technique of constant withdrawal of blood from the hepatic portal vein after drug administration into the gastrointestinal tract, it was shown the norethindrone is metabolized in the gut wall. Hence, in the rat at least, there are both intestinal and hepatic components of the overall first-pass effect. In addition, increasing the time of intraportal injection from 15 sec to 2 min (thereby reducing the rate of drug delivery to the liver) resulted in the AUC being reduced by 40%. Dose-dependent kinetics were observed with doses of norethindrone greater than 500 microgram/kg.

Administration, Oral↗
PubMed1977

Yersiniosis in captive exotic mammals.

Within a 2 1/2-month period, Yersinia pseudotuberculosis infection occurred in 3 blesbok (Damaliscus dorcas), 1 dik-dik (Madoqua kirkii), and 1 giant anteater (Myrmecophaga tridactyla) at the National Zoological Park, Washington, DC. Lesions consisted of fibrinonecrotic enteritis and peritonitis, mesenteric lymphadenitis, and embolic pyogranulomatous lesions in the liver, spleen, and lungs. Feed contaminated with the feces of wild rats and pigeons was thought to be the source of infection.

Animals↗
PubMed1977

Lead poisoning in sandhill cranes.

Seven Florida sandhill cranes (Grus canadensis pratensis) and 6 greater sandhill cranes (Grus canadensis tabida) were exposed to lead-base paint containing 27% lead. One bird of each subspecies died enroute to the hospital, with a clinical history of anorexia, weakness, and open-mouth breathing of 36 hours' duration. There were no gross lesions, and microscopic lesions were limited to focal hepatic necrosis and hemosiderosis. Two of each subspecies of cranes developed clinical signs of lead poisoning, which included anorexia, weakness, green diarrhea, regurgitation, and open-mouth breathing. Diagnosis of lead poisoning was confirmed on the basis of blood lead concentrations ranging from 146 microgram/100 ml to 378 microgram/100 ml. These 4 cranes were treated successfully with calcium disodium edetate intramuscularly. Seven of the birds remained clinically normal despite high blood lead levels, especially in the greater sandhill cranes.

Animals↗
PubMed1977

Genetic control of lymphocyte activation: lack of response to low doses of concanavalin A in lipopolysaccharide-nonresponder mice.

C3H/HeJ mice do not respond to the polyclonal B-cell activator lipopolysaccharide (LPS) from Escherichia coli; this was first described by Sultzer who observed that mice of this strain did not respond to an intraperitoneal (i.p.) injection of LPS as measured by the accumulation of leukocytes in the peritoneal cavity. Neither were C3H/HeJ mice as susceptible to LPS toxcitiy (1). It was later reported that LPS-induced mitogenesis (2,3), adjuvanticity (4), and the appearance of Ia antigens on B lymphocytes as induced by LPS, (5) was also absent in C3H/HeJ mice. However, lymphocytes from these mice respond normally to the polyclonal B-cell activators purified protein derivative of tuberculin (2,6) and dextran sulfate and have also been reported to respond normally to concanavalin A (Con A) (2). Furthermore, the immune responses to sheep erythrocytes (7) and soluble thymus-dependent antigens (4) are normal in C3H/HeJ mice. Unresponsiveness to LPS in C3H/HeJ mice has been found to Be due to a defect in a single gene or a set of linked genes (3,8) which has been mapped between the major urinary protein locus and the locus coding for polysyndactyly on chromosome 4. (1) We have reported that injection of LPS into mice of an LPS-responsive strain causes a shift in the Con A dose-response curve of cultured spleen cells, suppressing the low does response (9). Therefore, we tested the Con A proliferative response in cultures of normal or LPS-activated spleen cells from LPS-responder (C3H/Tif) and LPS-nonresponder (C3H/HeJ) mice. We report here that C3H/HeJ spleen cells respond poorly to low concentrations of Con A (0.05-0.1 mug/ml). Injection of LPS 2 days before culture inhibits the response to low doses of Con A in cultures of C3H/Tif spleen cells but has no inhibitory effect on the dose response profile of C3H/HeJ spleen cells. Furthermore, the low dose Con A response of spleen cells is dependent upon the presence of an Ia-positive cell. (2) The role of Ia-positive cells in the Con A response of C3H/Tif and C3H/HeJ spleen cells is described.

Animals↗
PubMed1977

Utility of ultrasound in the differential diagnosis of acute cholecystitis.

Three case reports show the usefulness of ultrasound examination in patients with right upper quadrant masses despite clinical or roentgenographic evidence of cholecystitis or cholelithiasis. In one patient an hepatic fungal abscess from Candida albicans was distinguished from the gallbladder; in another, the same was possible for a pyogenic abscess in an old surgical incision; and in a third, extension of a gallbladder carcinoma to the liver was distinguished from the gallbladder itself. Thus, the ultrasound examination allowed assessment of the relationship between the clinically palpable mass and ultrasonically defined anatomy, When needed, increased specificity of diagnosis was obtained by ultrasonically guided fine-needle aspiration biopsy.

Adult↗
PubMed1977

A combination of chlorambucil, vinblastine, procarbazine and prednisolone for treatment of Hodgkin's disease.

Seventy patients with Hodgkin's disease have been treated with a combination of chlorambucil, vinblastine, procarbazine and prednisolone (Ch1VPP). The complete remission rate of 75-7% compares well with that produced by other combinations. The combination is non-toxic, easily administered and can be given safely to outpatients. Its main advantage is that it is far less upsetting to patients than combinations containing nitrogen mustard.

Adolescent↗
PubMed1977

Elevated serum IgE and IgG4 in patients with atopic dermatitis.

The quantitative measurement of the IgE and IgG subclass levels in the sera of 29 patients with atopic dermatitis has revealed significantly elevated levels of IgE and IgG4 in a relatively high proportion of patients with this condition compared to non-atopic patients with warts and to a group of normal volunteers studied previously. The possible significance of these observations is discussed in relation to current evidence suggesting the involvement of IgG4 in certain immediate-type hypersensitivity disorders.

Adolescent↗
PubMed1977

Polymyxins as inhibitors of polyclonal B-cell activators in murine lymphocyte cultures.

The polymyxin antibiotics polymyxin B sulfate and colistin methane sulfonate were examined for their ability to inhibit responses to the polyclonal B-cell activators (PBA) bacterial lipopolysaccharide (LPS), dextran sulfate (DS), pneumococcal polysaccharide (SIII), and purified protein derivative of tuberculin (PPD) in spleen cell cultures. Polymyxin concentrations of 1 and 10 microng/ml significantly inhibited both the deoxyribonucleic acid synthetic and polyclonal antibody responses stimulated by LPS, DS, and SIII. At these concentrations of polymyxins, responses to PPD and to the T-cell mitogens concanavalin A and phytohemagglutinin were not affected. Inhibition was not caused by a generalized lymphocyte toxicity. After dialysis of LPS-polymyxin and DS-polymyxin mixtures, the PBA preparations showed decreased mitogenic activity. Thus, the polymyxins probably interacted directly with the LPS and DS molecules. The mitogenic response to DS was more significantly inhibited than the response to a nonsulfated dextran. The cationic property of the polymyxins probably allows attachment to negatively charged groups in the mitogenically relevant parts of some but not all PBA molecules,, this attachment resulting in the loss of PBA activity.

Animals↗
PubMed1977

Myasthenia gravis: steroid-induced effects on lymphocyte subpopulations in myasthenia gravis.

Lymphocyte subpopulations from patients with myasthenia gravis were evaluated during chronic steroid therapy. A marked lymphocytopenia (10-70%) was initially (day 3-21) noticed as well as a preferential depletion of thymus-derived cells which paralleled the clinical deterioration. Thus there was a relative increase in B cells, although their absolute number remained rather constant. These changes were reverted within 2-4 weeks in spite of continuous treatment. These findings are compatible with a release of myasthenic factors (anti-acetylcholine receptor antibodies?) during the initial steroid-induced cell damage, the long-term beneficial effects being due to loss or suppression of autoreactive helper t cells.

Adolescent↗
PubMed1976

Tuberculosis in captive exotic birds.

Avian tuberculosis was studied clinically and pathologically in 137 affected birds from the National Zoological Park during a 7-year period (1969-1975). Twelve of 22 orders exhibited were affected by the disease, and the highest annual mortality was 4% (in 1975). Antemortem diagnosis of early cases of the disease, based on tuberculin testing, and serologic, hematologic, and radiographic studies, was inconsistent and often not conclusive. Pathologically, the diseases primarily involved digestive organs and spleen. There was a spectrum of lesions consisting of nodules of large foamy histiocytes packed with acid-fast bacilli to giant cell-containing granulomas that were often caseous but not cavitated or calcified. Amyloidosis was seen in approximately 20% of the cases. Mycobacterium avium serotype 1 was isolated from 30 tuberculous birds cultured. There was no sex predilection, and most of the affected birds were adults ranging from 1 to 10 years of age.

Animals↗
PubMed1976

The effect of membrane stabilizing agents on induction of the immune response. I. Effect of lymphocyte activation in mixed lymphocyte reactions.

The effect of three membrane-stabilizing agents, chlorpromazine, imipramine, and lidocain, on in vitro activation of cellular responses was studied using the one-way MLR. Cellular activation was found to be depressed by these drugs. However, the degree of suppression paralleled the decline of viable cells in the cultures. It is concluded that drug-induced inhibition of MLR was due solely to the toxicity of the compounds.

Animals↗
PubMed1976

Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.

Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.

Animals↗
PubMed1976

Association between mitogenicity and immunogenicity of 4-hydroxy-3,5-dinitrophenacetyl-lipopolysaccharide, a T-independent antigen.

Polymyxin B, which is a basic polypeptide produced by various strains of Bacillus Polymyxa, has previously been shown to prevent the lethal effect of LPS and to neutralize the Schwartzmann reaction. In this study we have investigated the interactions between polymyxin B and lipopolysaccharide (LPS) and hapten LPS conjugates. Polymyxin B was found to suppress mitogenicity of LPS and also to inhibit immunogenicity of the hapten conjugate 4-hydroxy-3,5-dinitrophenacetyl (NNP)-LPS. Inhibition was not due to interference with the expression of NNP determinants nor to cross-reactivity between PB and the hapten. Since mitogenicity and immunogenicity decreased in parallel, we conclude that B-cell activation in specific thymus independent responses does not take place in the absence of a nonspecific (non-Ig-mediated) signal.

Animals↗