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Biomedical subjects

R T Nelson

Publications and source records attributed to R T Nelson.

17 recordsLinked to original sources
PubMed1996

Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.

The islet in non-insulin-dependent diabetes mellitus (NIDDM) is characterized by loss of beta cells and large local deposits of amyloid derived from the 37-amino acid protein, islet amyloid polypeptide (IAPP). We have hypothesized that IAPP amyloid forms intracellularly causing beta-cell destruction under conditions of high rates of expression. To test this we developed a homozygous transgenic mouse model with high rates of expression of human IAPP. Male transgenic mice spontaneously developed diabetes mellitus by 8 weeks of age, which was associated with selective beta-cell death and impaired insulin secretion. Small intra- and extracellular amorphous IAPP aggregates were present in islets of transgenic mice during the development of diabetes mellitus. However, IAPP derived amyloid deposits were found in only a minority of islets at approximately 20 weeks of age, notably after development of diabetes mellitus in male transgenic mice. Approximately 20% of female transgenic mice spontaneously developed diabetes mellitus at 30+ weeks of age, when beta-cell degeneration and both amorphous and amyloid deposits of IAPP were present. We conclude that overexpression of human IAPP causes beta-cell death, impaired insulin secretion, and diabetes mellitus. Large deposits of IAPP derived amyloid do not appear to be important in this cytotoxicity, but early, small amorphous intra- and extracellular aggregates of human IAPP were consistently present at the time of beta-cell death and therefore may be the most cytotoxic form of IAPP.

Aging↗
PubMed1995

Antistaphylococcal activity of rifampin-bonded gelatin-impregnated Dacron grafts.

The affinity of rifampin to bond to Dacron permits implantation of a vascular prosthesis with anti-staphylococcal bioactivity. The performance of rifampin-bonded Dacron grafts was evaluated in vitro and in vivo to develop a bonding technique with optimal graft bioactivity which was then used for in situ reconstruction of a biofilm graft infection. In vitro bioactivity was measured at 24-hr intervals for three types of Dacron prostheses (plain, gelatin, and collagen-impregnated) exposed to rifampin at varied concentrations and immersion times. Gelatin-impregnated grafts demonstrated superior bioactivity (P < 0.05). Rifampin concentration and graft type had a greater effect on bioactivity than immersion time (P < 0.01). Gelatin-impregnated grafts immersed in a 60 mg/ml rifampin solution for 15 min produced optimum bioactivity. Six grafts prepared in this fashion were used to replace the canine aorta. The level and duration of in vivo antistaphylococcal activity to Staphylococcus aureus and Staphylococcus epidermidis were less (P < 0.05) than those measured in vitro, but rifampin levels exceeded the study strain maximum inhibitory concentration for up to 48 hr. In a canine model, the rifampin-bonded gelatin-impregnated (N = 14) or nonbonded control (N = 10) grafts were used as in situ replacement for an established aortic graft infection caused by S. epidermidis. Replacement with a rifampin-bonded graft resulted in successful anatomic healing of perigraft and anastomotic tissue. Persistent biofilm colonization was confirmed in 8 of 10 controls versus 4 of 14 rifampin-bonded grafts (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

AGD/ADA.

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American Dental Association↗
PubMed1991

Characterization of bovine haemopoietic progenitor cells using monoclonal antibodies and fluorocytometry.

Monoclonal antibodies against bovine leucocyte cell surface differentiation antigens were used in combination with a fluorescence activated cell sorter to enrich bovine haemopoietic progenitor cells present in bone marrow cell populations prior to in vitro culture. After two sequential centrifugations of the bone marrow cell suspension through Ficoll-Paque, the interface fraction was stained with a cocktail of monoclonal antibodies directed against mature monocytes/macrophages, granulocytes and lymphocytes. Using appropriate electronic window settings on a FACStar Plus, cells with a high 90 degrees light scattering property (granular cells), a low forward light scattering property (erythrocytes and reticulocytes) and cells positive for monoclonal antibodies specific for lineage-restricted leucocyte markers were removed and the negative cell fraction collected. These negatively-selected cells were stained with monoclonal antibodies specific for a pan-leucocyte or a MHC class II marker and the positive cell population was collected in a second sort and subsequently submitted to culture. All erythroid and granulocyte/macrophage colony forming cells expressed MHC class II antigens, as well as the pan-leucocyte antigen. These same progenitors did not bind any of a variety of monoclonal antibodies directed against lineage-specific antigens on lymphocytes, granulocytes or monocytes/macrophages, although they did bind monoclonal antibodies recognizing MHC class I antigens. Between 85% and 91% of the isolated cells seeded were capable of forming erythroid or granulocyte/macrophage colonies within 5 to 10 days, thus increasing the plating efficiency of these cell types in bone marrow populations by at least 60 fold.

Animals↗
PubMed1990

Bovine erythroid (CFU-E, BFU-E) and granulocyte-macrophage colony formation in culture.

Progenitor cells of bovine erythrocytes, megakaryocytes, and granulocyte-macrophages were cultured in agar or methylcellulose media. Colony formation was supported by cell-free conditioned medium from short-term cultures of concanavalin A-stimulated bovine peripheral blood leukocytes. Granulocyte-macrophage progenitors proliferated well in both types of semisolid culture media, giving rise to neutrophils (from granulocyte colony-forming units, CFU-G), eosinophils (from eosinophil CFU, CFU-Eo), monocyte-macrophages (from macrophage CFU, CFU-M), and mixed granulocyte-macrophages (from granulocyte-macrophage CFU, CFU-GM). Better growth of megakaryocytes, as well as late (erythroid CFU, CFU-E) and early (erythroid burst-forming units, BFU-E) erythroid progenitors was obtained with methylcellulose. Despite considerable variation in the numbers and types of colonies formed from different aspirates of bovine marrow, the numbers observed were generally comparable to those obtained from human and mouse bone marrow cells. The proliferation of bovine BFU-E and eosinophil progenitors herein described is the first successful report of the culture of these cell types.

Animals↗
PubMed1988

Attempts to protect goats against challenge with Trypanosoma vivax by initiation of primary infections with large numbers of metacyclic trypanosomes.

Attempts were made to immunize goats by infection with large numbers of metacyclic trypanosomes of a clone of Trypanosoma vivax, followed by chemotherapy. Five groups of 6 goats each were infected intradermally with 5 different doses of cultured metacyclics of T. vivax, ranging from 10(2) to 10(6) trypanosomes/goat. Four weeks after infection, the goats were treated with 10 mg/kg diminazene aceturate (Berenil, Hoechst A.G.). Three weeks after treatment, 3 goats in each group were challenged intradermally with 10(4) homologous metacyclics derived from culture. The remaining 3 goats in each group were challenged by 20 tsetse infected with the homologous clone. Five out of 30 goats were resistant to homologous challenge; 4 of the goats that had been challenged with culture parasites, and 1 that had been challenged by tsetse. In each group 1 goat was protected. Protection was therefore not apparently influenced by the number of trypanosomes used to establish the primary infection. In another experiment, 6 goats were each infected by feeding 100 tsetse on the goats for 15 consecutive days. Three weeks after infection the goats were treated with Berenil and 3 weeks later challenged by 20 tsetse infected with the homologous clone. Three out of the 6 goats resisted challenge. The susceptible goats in both experiments, however, showed a reduction in the peak of parasitaemia following challenge compared with both challenge controls and the initial infections. Lytic antibodies to cultured metacyclics of T. vivax were detected in goats that resisted challenge after a primary infection with cultured metacyclics, and in resistant and susceptible goats after a primary infection by tsetse. All infected goats produced lytic antibodies to live bloodstream forms, as well as antibodies to bloodstream form lysates (demonstrated by ELISA). It is suggested that the immunity that had been induced in some of the experimental animals is due to antibody responses to both metacyclic and bloodstream variable antigen types (VATs) expressed during infection.

Animals↗
PubMed1988

Ro 15-0216: a nitroimidazole compound active in vitro against human and animal pathogenic African trypanosomes.

In vitro systems for the continuous cultivation of Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. congolense and T. vivax were used to determine the antitrypanosomal activity of the 2-substituted nitroimidazole Ro 15-0216. For all trypanosome species, the concentration which inhibited parasite growth by 50% (IC50 value) was established: 0.0957 microgram ml-1 (T. b. brucei TC221), 0.1327 microgram ml-1 (T. b. gambiense STIB 754-A), 0.0450 microgram ml-1 (T. b. rhodesiense STIB 704-BABA), 0.0896 microgram ml-1 (T. congolense ILNat 3.1) and 0.0109 microgram ml-1 (T. vivax ILRAD 1392). The IC50 value of its major metabolite Ro 19-9638 was 0.0341 microgram ml-1 (T. b. rhodesiense STIB 704-BABA). Furthermore, minimum exposure times required to render T. b. brucei non-infective for mice as well as preventing their growth in vitro have been established to be three, four, six and ten hours at drug concentrations of 30, 10, 3 and 1 microgram ml-1, respectively.

Acetanilides↗
PubMed1988

Chigger relief.

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Animals↗
PubMed1987

Cell adhesion in Trypanosoma: in vitro studies of the interaction of Trypanosoma vivax with immobilized organic dyes.

Certain bloodstream forms of Trypanosoma vivax have been shown to attach to Amicon Matrex Gel Green A dye beads in a manner similar to the in vivo binding of T. vivax to the inner surface of the tsetse fly proboscis. We now report an in vitro assay for trypanosome-bead attachment and show that only the 9,10-anthraquinone portion of the dye molecule is involved in the binding of trypanosomes to beads and that bead-bound dyes with similar structures also support binding to differing degrees. The binding is dependent upon the amount of dye on the beads and this, and other evidence, suggests that an array of dye molecules, rather than individual molecules, may be the actual recognition site. Various external effectors, including temperature, soluble protein-dye complexes, and serum of mice with chronic T. vivax infections, reduce trypanosome binding, indicating that at least one immunogenic trypanosome macromolecule is involved. The trypanosome-bead interaction mimics the in vivo binding to tsetse proboscis and warrants closer examination as a model of trypanosome cell adhesion in the tsetse fly.

Animals↗
PubMed1984

Titration in cattle of infectivity and immunogenicity of autologous cell lines infected with Theileria parva.

Cell lines infected with Theileria parva were derived by infection of bovine peripheral blood lymphocytes with sporozoites in vitro. Cattle were inoculated with doses of autologous infected cells ranging from 1 X 10(1) to 1 X 10(8). Infection became established in animals which received 1 X 10(2) or more cells. While 1 X 10(2) cells resulted in sub-patent infection with development of immunity to challenge with sporozoites, larger doses of cells gave rise to patent infections of increasing severity. Thus, doses of 1 X 10(5) and 1 X 10(6) cells sometimes produced lethal infections and with 1 X 10(7) and 1 X 10(8) the outcome was invariably lethal. Based on the previous observation that induction of immunity by allogeneic cells requires transfer of infection into the recipient-host cells, a comparison of the infections produced by autologous and allogeneic cells indicated that the transfer of infection from allogeneic cells occurs at a frequency of maximally 1 X 10(-5). Two pairs of cattle were identified as being mutually non-reactive in the mixed leukocyte reaction (MLR). Doses of 1 X 10(6) and 1 X 10(7) cells of cell lines derived from 1 animal of each pair were inoculated into the autologous host, the non-reactive partner and an animal which was shown to be strongly reactive to the donor in the MLR. In each instance, the reaction in the MLR non-reactive recipient was not significantly different from that of the MLR reactive recipient, but was markedly different from that of the autologous recipient.

Animals↗
PubMed1982

Generation of cell-mediated cytotoxicity to Theileria parva (East Coast fever) after inoculation of cattle with parasitized lymphoblasts.

The participation of genetically restricted cell-mediated lympholysis (CML) in protective immunity against Theileria parva was examined in cattle inoculated with autologous and allogeneic parasitized lymphoblasts. The majority of cattle given 10(7) infected allogeneic cells were protected against infection with the homologous parasite. Animals inoculated with drug-cured lymphoblasts, normal allogeneic lymph node cells (LNC), or a combination of LNC and parasitized allogeneic cells were fully susceptible. The magnitude of the primary CML responses against autologous infected targets (as opposed to that against the allogeneic lymphoblasts inoculated or 3rd-party targets) more accurately correlated with a decreased severity of infection after challenge. Autologous CML responses appeared earlier as cattle were given increasing numbers of parasitized autologous lymphoblasts, and were higher and more persistent with increasing parasitosis. Between 10(2) and 10(5) autologous infected cells induced immunity to T. parva, whereas at least 10(7) allogeneic lymphoblasts were required for comparable protection. The findings provide additional evidence for a protective role of restricted CML responses against T. parva in vivo. When allogeneic infected cells are used for immunization, viable T. parva need to establish infection in host cells to induce adequate protective immunity.

Animals↗
PubMed1981

Cell-mediated immune responses to Theileria parva (East Coast fever) during immunization and lethal infections in cattle.

Leucocytes from cattle with lethal or sub-lethal infections with Theileria parva were examined for responses in autologous mixed lymphocyte reactions (MLR) and for specific and non-specific cytotoxicity against cultured cell lines. During lethal infections, lymphoblasts isolated from central lymph from days 8 to 14 stimulated proliferation in autologous lymphatic lymphocytes and peripheral blood leucocytes (PBL), although cytotoxicity was not generated in such cultures. After day 14, non-specific cytotoxicity was exhibited by both lymphocyte populations and was maximal in moribund calves. Non-specific lytic activity was also noted in PBL from recovering calves, but disappeared after the elimination of the parasite. Calves immunized against T. parva by the concurrent administration stabilate and long-acting tetracycline showed macroschizont forms of the parasite in host lymphocytes from days 15 to 18 after infection. During this period, lymph node cells from infected calves stimulated MLR-type responses in autologous PBL. However, PBL from immunized calves lysed directly, autologous infected lymphoblasts in a genetically-restricted fashion from days 14 to 21, although additional cytotoxicity was not generated in the MLR. The results imply that when the parasitosis of T. parva is curtailed, specific cell-mediated responses are mounted against parasite-induced antigens in combination with polymorphic host antigens on the leucocyte membrane. These reactions are probably the major immune responses conferring to recovered cattle, immunity against rechallenge with the homologous isolate of T. parva.

Animals↗
PubMedDate not supplied

Effects of chicken anemia agent on lymphokine production and lymphocyte transformation in experimentally infected chickens.

One-day-old chicks with no maternal antibodies to chicken anemia agent (CAA) were inoculated intramuscularly with CAA grown in MDCC-MSB1 cells. A control group of birds from the same source was inoculated intramuscularly with a lysate from uninfected MSB1 cells. Birds were killed at 8, 15, 22, 29, and 43 days postinoculation (PI), and the spleens were removed. Spleen cells were dispersed and stimulated with various concentrations of Concanavalin A (Con A), and lymphocyte transformation responses were determined. Supernatants from Con A-stimulated cultures were assayed for T-cell growth factor (TCGF) and interferon. Decreased lymphocyte transformation and TCGF production were demonstrated at 8 and 15 days PI. This was followed by a stimulation in activities before a return to control levels at 43 days PI. Interferon levels were elevated 8 days after infection. This was followed by a significant decrease in activity compared with controls at 15, 22, and 29 days PI, and a return to control levels by 43 days PI. The results suggest that CAA infection in young chickens can produce a dramatic decrease in immune competence, which, although transitory, is likely to seriously compromise the ability of birds to mount a successful immune response to invading pathogens.

Anemia↗