Biomedical subjects
Publications and source records attributed to D N Reddy.
Endoscopic Hemoclips were developed as a method of securing permanent hemostasis in cases of nonvariceal gastrointestinal bleeding. However, Hemoclips have also been found useful in several other situations, such as closure of small perforations, as marking devices, and for anchoring feeding tubes. We describe here a further novel use of Hemoclips--to anchor an esophageal endoprosthesis.
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The effects of virus dose on host response were evaluated for the PPR strain of feline immunodeficiency virus (FIV-PPR). Specific pathogen-free cats were inoculated intravenously with 50, 250 or 1250 TCID(50) of FIV-PPR. Two weeks after inoculation, virus was detected in 10(6) peripheral blood mononuclear cells (PBMCs) of all infected animals, and the CD4(+):CD8(+) T lymphocyte ratios fell from greater than 2 to approximately 1 in all infected animals within the first 8 weeks after infection. Provirus detected in all groups using PCR and 10(3) PBMC was biphasic. Nine of 15 animals were positive between weeks 2 and 4 p.i. and 14 of 15 were positive by week 8 p.i. Transient lymphadenopathy was detected in most cats receiving 1250 TCID(50) and the 250 TCID(50) of virus, whereas no lymphadenopathy was detected in the 50 TCID(50) group or the five uninfected cats. Animals that had received the largest dose seroconverted earliest (on average at week 4.0) and those receiving the least seroconverted last (on average at week 5.6). Neither neutropenia nor lymphopenia were detected. FIV-specific CTL responses of memory effector cells could be detected in animals receiving all three doses but was highly variable among individual animals. Neurological manifestations determined after 15 weeks p.i. were observed in most infected cats, including two of the three that had received 50 TCID(50) of virus. However, the observed neurologic abnormalities were markedly less severe in the animals receiving the least amount of virus. Therefore, lymphadenopathy and neurologic signs of illness were less severe and seroconversion was slower in the animals that received the lowest dose compared with those receiving the 250 and 1250 TCID(50) doses of the FIV-PPR strain.
The efficacy and safety of a gene-deleted bovine herpesvirus-1 (BHV-1) vaccine was determined in a bovine herpesvirus challenge trial in calves. Three different doses of the vaccine were administered intramuscularly at 10(5), 10(6) and 10(7) PFU/ml and compared to a commercial vaccine and non vaccinated control calves. Challenge was performed by intranasal aerosolization with the Cooper strain of BHV-1 (3 x 10(4) PFU/ml). The non-vaccinated calves shed significantly (P < 0.05) more virus than all other groups on days 4, 8 and 10 post challenge. By day 14 post challenge, antibody titers for BHV-1 of calves vaccinated with 10(7) PFU/ml were significantly (P < 0.05) higher than the commercial or non-vaccinated calves. Clinical scores of non-vaccinated calves were significantly (P < 0.05) higher than all other groups on days 4-14 post challenge. With both radioimmunoprecipitation and competitive enzyme-linked immunosorbent assays (C-ELISA), calves in the gene-deleted vaccine groups mounted comparable specific responses against gB, gC and gD post vaccination as calves in the commercial vaccine group, but in a dose dependent manner. These data suggest that the gene-deleted BHV-1 vaccine tested may be used as an effective vaccine in controlling BHV-1 infections.
We investigated the potential of a herpesvirus of turkey (HVT)-based recombinant virus (rHVT) as an in ovo vaccine to protect specific-pathogen-free chickens against Newcastle disease (ND) and Marek's disease (MD). The rHVT, designed to express fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of the lentogenic Hitchner B1 strain of ND virus (NDV), as well as glycoproteins A and B of the GA strain of serotype 1 MD virus (MDV) was efficacious in protecting chickens against ND and MD. No adverse effects on hatchability or the survival of chickens were observed following in ovo vaccination with rHVT. A single administration at embryonation day 18 (ED18) or at hatch protected chickens against challenge-exposures with virulent MDV strain RB-1B and velogenic NDV strain GB-Texas (NDV-GB-TX). Vaccinated chickens developed antibodies against both viruses as detected by serological tests, namely, hemagglutination inhibition, virus neutralization and western immunoblotting for NDV, and immunofluorescence and radioimmunoprecipitation assays for MDV. PCR analysis showed that in ovo vaccination with rHVT resulted in a persistent infection leading to systemic immunity against ND for up to 8 weeks of age, the longest period of time tested in this study. However, virus isolation tests indicated that rHVT-vaccinated chickens were only partially protected from the replication of NDV-GB-TX in the trachea. The results of the study indicate that rHVT is safe for both ED18 and posthatch vaccination for ND and MD, and because the vaccine persists, it may induce longer lasting immunity than conventional live NDV vaccines.
An experiment was conducted to determine the adjuvanticity of recombinant bovine IL-1 beta (rBoIL-1 beta) and recombinant bovine IL-2 (rBoIL-2) administered in conjunction with a single Streptococcus suis vaccination in pigs. Sixty 4-week-old pigs were allotted to eight groups: nonvaccinated controls; vaccinated controls; rBoIL-beta at 0.1, 1, and 10 micrograms kg-1; rBoIL-2 at 2.5, 25, and 250 micrograms kg-1. All pigs (except nonvaccinated controls) were vaccinated on Day 0 with a commercial Streptococcus suis vaccine (serotypes 1 and 2). At vaccination, pigs were injected intramuscularly with their respective cytokine treatments. Pigs received additional cytokine injections on 2 consecutive days. On Day 21, all pigs were challenged intravenously with 3.2 x 10(9) colony forming units of a log phase culture of S. suis (serotype 2). The highest dose of rBoIL-1 beta exceeded the maximum tolerable dose for the cytokine; however, this dose of rBoIL-1 beta protected pigs from the S. suis challenge. Pigs administered rBoIL-1 beta at 10 micrograms kg-1 had higher antibody responses to S. suis, less severe clinical signs of the disease after challenge, better growth performance during the infection, and less severe gross pathological lesions caused by the bacteria. No pigs in this treatment group died from the bacterial challenge. These data suggest that rBoIL-1 beta (10 micrograms kg-1), administered intramuscularly for 3 consecutive days at vaccination, is more effective than a single S. suis vaccination alone in protecting pigs against a S. suis challenge.
The safety and efficacy of a fowlpox-Newcastle disease vaccine were evaluated by in vitro and in vivo methods. Genetic and phenotypic stability following cell culture and chick passage were demonstrated. The safety characteristics of the recombinant virus equalled or exceeded those of the parent fowlpox virus, as determined by lack of shed and spread to contacts, failure to revert to virulence following passage in chicks and innocuity in other avian species. The fowlpox-Newcastle Disease virus effectively immunized against virulent fowlpox challenge and virulent Newcastle disease challenge (intramuscular or intra-ocular administration). These results indicate that the recombinant FPV/NDV virus is a safe and effective vaccine for poultry.
We describe the preparation of monoclonal antibodies (Mabs) directed against recombinant bovine interleukin-1 beta (rBoIL-1 beta). These anti-IL-1 beta Mabs were designated SA10, SA12, SA13, SA15, and SA22, and were characterized on the basis of their epitope specificity and cross-reactivity with homologous and heterologous cytokines in enzyme-linked immunosorbent assays and immunoblot analyses. Additionally, the ability of these Mabs to neutralize IL-1 beta was tested in thymocyte costimulation assays. The ELISA titers of all Mabs ranged from 9.4 x 10(6) to 1 x 10(7). Data indicate that Mabs SA10, SA12, SA15, and SA22 neutralized both bovine macrophage-derived IL-1 (1:4) and rBoIL-1 beta (1 ng ml-1). All the Mabs against rBoIL-1 beta (SA10, SA12, SA13, SA15, SA22) were specific and did not cross-react with other cytokines tested, except recombinant human IL-1 beta (rHuIL-1 beta). This finding suggests that these Mabs recognize epitopes common to human and bovine IL-1 molecules. Competition experiments suggested that Mab SA22 recognized a different epitope and Mabs SA10, SA12, SA13, and SA15 recognized the same epitope on the rBoIL-1 beta molecule. These observations suggest that these Mabs could be useful reagents for developing immunoassays to measure bovine IL-1 beta from biological fluids and to study the immunoregulatory role of IL-1 in the bovine immune system.
Three experiments, using 85 crossbred beef calves, were conducted to evaluate the adjuvanticity of single, multiple, and combined doses of recombinant bovine IL-1 beta (rBoIL-1 beta) and recombinant bovine IL-2 (rBoIL-2), with a modified-live bovine herpesvirus-1/parainfluenza-3 (BHV-1/PI-3) virus vaccine and a killed bovine viral diarrhea (BVD) virus vaccine. Cytokines were administered intramuscularly at vaccination but at different injection sites. All cytokine treatments increased non-major histocompatibility complex (MHC)-restricted cytolytic capability of peripheral blood mononuclear cells (PBMC) against virus-infected target cells and serum neutralizing (SN) antibody titers to BHV-1 and BVD virus. Multiple, consecutive injections of rBoIL-2 generally showed the greatest adjuvant effect, and no additive effect was observed when rBoIL-1 beta and rBoIL-2 were administered together. In a challenge experiment, calves were vaccinated with a modified-live BHV-1/PI-3 vaccine and infected with BHV-1 on Day 21. Cytokine-treated calves had higher SN antibody titers to BHV-1 than did the control calves at the time of challenge. Calves that were administered rBoIL-2 on 5 consecutive days shed less BHV-1 and had the highest SN antibody titer to BHV-1 (Day 28). These data suggest that rBoIL-1 beta and rBoIL-2 may be useful immunoadjuvants for bovine respiratory disease virus vaccines.
Bovine immune responses to rabbit antiidiotypic antibodies (anti-Id) against neutralizing monoclonal antibodies to bovine herpesvirus-1 (BHV-1) envelope glycoproteins and to BHV-1 glycoproteins were compared. Glycoprotein-immunized animals produced high titers of anti-BHV-1 antibodies and were protected against BHV-1 challenge. Recombinant bovine interleukin-2 (rIL-2)-treated, anti-Id-immunized animals showed a slight reduction in clinical disease, and one calf produced BHV-1-neutralizing antibodies. Treatment with rIL-2 augmented non-BHV-1-specific immune responses. However, even with rIL-2 as an adjuvant, the mixture of polyclonal anti-Id did not elicit a consistent, protective BHV-1-specific immune response in calves.
The effect of pre- and postweaning exposure to soybean meal on postweaning growth performance and immune response by the early-weaned pig was analyzed. In Exp. 1, treatments were assigned in a 2 x 2 x 2 factorial arrangement. Pigs were derived from gilts fed either a soybean meal- or a corn gluten meal-based diet during gestation and lactation. Six to eight pigs per litter were either stomach-infused with or without (placebo) soybean meal during d 5 to 9 after farrowing. At weaning, 240 pigs (initially 5.1 kg, 21 +/- 1 d) were randomly allotted to either a corn-soybean meal or a corn-dried skim milk-dried whey diet based on gilt and infusion treatments. Average daily gain, ADFI, and gain:feed ratio were decreased (P < .05) on d 0 to 14 postweaning for pigs fed a soybean meal diet compared with pigs fed a milk diet. Skin-fold thickness after intradermal injection of soy protein and casein extracts on d 6 and measured on d 7 postweaning was not affected (P > .10) by dietary treatment, but serum immunoglobulin G titers to soybean glycinin and beta-conglycinin were increased (P < .01). From d 14 to 35 postweaning, all pigs were fed a common (1.25% lysine) corn-soybean meal diet containing 10% dried whey. Average daily gain, ADFI, and gain:feed ratio were decreased (P < .05) from d 14 to 35 for pigs fed a milk diet on d 0 to 14 postweaning. Serum immunoglobulin G titers were higher (P < .01) on d 21 postweaning for pigs fed soybean meal for the entire nursery period. Cumulative ADG (d 0 to 35) and gain:feed ratio were decreased (P < .05) for pigs fed a milk diet from d 0 to 14 compared with pigs fed a soybean meal diet. In Exp. 2, 104 pigs (initially 5.3 kg, 21 +/- 1 d of age) were used to determine the effect of 0, 7.5, 15.0, and 22.5% soybean meal in a high-nutrient-dense starter pig diet. Differences were not detected (P > .10) in ADG, ADFI, and gain:feed ratio during d 0 to 14, but ADFI decreased (linear, P < .05) and gain:feed ratio increased (linear, P < .05) during d 14 to 35 and for the entire 35-d trial as the level of soybean meal increased.(ABSTRACT TRUNCATED AT 400 WORDS)
A study was conducted in dairy cows to evaluate the efficacy of recombinant bovine interleukin 2 (rBoIL-2) as an adjunct to antibiotic therapy in Staphylococcus aureus mastitis. In normal, non-mastitic cows, intramammary infusion of rBoIL-2 caused a tenfold increase in somatic cell counts (SCC) in milk. Co-administration of 2 mg of rBoIL-2 and sodium cephapirin in cows with established S. aureus mastitis decreased SCC and shedding of S. aureus compared with values from cows that were given only sodium cephapirin or 10 mg rBoIL-2 with sodium cephapirin. Cows in the 2 mg rBoIL-2 group cleared the infection earlier and at 2 weeks after treatment had not relapsed with staphylococcal mastitis. These data suggest that rBoIL-2 may be useful as an immunotherapeutic agent in controlling mastitis.
In a double blind, multicenter, parallel group clinical trial in patients with symptomatic duodenal ulcers, 129 patients were randomized to receive either omeprazole 20 mg once daily (n = 65) or famotidine 40 mg once daily (n = 64) for 2 weeks, and if the ulcers were not healed, for a total of 4 weeks. Seventy four percent of these receiving omeprazole had healed ulcers after 2 weeks compared with 34.3% of those receiving famotidine (p < 0.001). At 4 weeks, the respective figures were 97.3% and 77.6% (p < 0.001). After 2 weeks of treatment, only 11.1% and 29.8% of omeprazole and famotidine treated patients respectively had day time pain (p < 0.02). Diary cards (successfully completed by 2/3rd of patients) showed that omeprazole treated patients required smaller amounts of antacids (p = ns). Over the first two weeks, ulcer healing rate was similar in smokers and non- smokers. No significant side effects were reported in either group. Omeprazole 20 mg/day provides more rapid relief of symptoms and heals a greater proportion of duodenal ulcers at 2 and 4 weeks than famotidine 40 mg/day.
Previously, we prepared rabbit anti-idiotypic (anti-Id) antibodies against murine monoclonal antibodies (MAbs) specific for the major bovine herpesvirus-1 (BHV-1) envelope glycoproteins. Glycoprotein III (gIII) contains neutralization epitopes and may be the virus attachment protein. Anti-Id antibodies to a neutralizing MAb that reacts with gIII were purified by sequential immunoaffinity chromatography. Immune responses to the purified anti-Id reagent and BHV-1 were compared in mice. Both groups of mice produced BHV-1-specific neutralizing antibodies. However, lymphocyte proliferative responses and interferon and interleukin-2 production were specific for the respective immunizing antigens. These results suggest that the anti-Id reagent may bear an internal image of a B-cell-stimulating epitope of glycoprotein gIII; however, this epitope does not stimulate a virus-specific cellular immune response in mice.
Recombinant bovine interleukin-1 beta (rBoIL-1 beta) was administered to calves in conjunction with a bovine herpesvirus-1 (BHV-1) vaccine. All calves were immunized against BHV-1 and three groups received rBoIL-1 beta at 33, 100, or 330 ng/kg on days 1 and 15; control animals received physiological saline. All calves were challenged with BHV-1 on day 22. Total leukocytes were increased by rBoIL-1 beta, primarily by causing neutrophilia and monocytosis; CD4/CD8 ratios tended to be increased in rBoIL-1 beta-treated animals. Serum neutralizing antibody titers and cytotoxic responses against BHV-1-infected bovine kidney fibroblasts were increased and virus excretion was decreased in rBoIL-1 beta-treated calves. On days 58 and 59, control and 100 ng/kg rBoIL-1 beta-treated calves were injected with dexamethasone (.04 mg/kg). Virus excretion was less and clinical signs of BHV-1 infection were lower in rBoIL-1 beta-treated calves after dexamethasone injection. These data suggest that rBoIL-1 beta may be an effective adjuvant to BHV-1 immunization.
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