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Biomedical subjects

F W Scott

Publications and source records attributed to F W Scott.

At least 73 records · Page 4Linked to original sources

Attempted immunisation of cats against feline infectious peritonitis using canine coronavirus.

Specific pathogen free kittens were vaccinated with an unattenuated field isolate of canine coronavirus (CCV) either by aerosol or subcutaneously, and received boosting vaccinations four weeks later. Aerosolisation elicited a homologous virus-neutralising (VN) antibody response that increased steadily over a four-week period and levelled off one to two weeks after revaccination. The initial aerosolised dose produced an asymptomatic infection with excretion of CCV from the oropharynx up to eight days after vaccination; virus shedding was not detected, however, after the second inoculation. Cats vaccinated subcutaneously developed low VN antibody titres after the first CCV dose and experienced a strong anamnestic response after the second dose. Neutralising antibody titres then levelled off one to two weeks after revaccination at mean values somewhat lower than in cats vaccinated by aerosol. CCV was not isolated from the oropharynx after either subcutaneous dose. Four weeks after CCV boosting inoculations, vaccinated cats and sham-vaccinated control cats were divided into three subgroups and challenged by aerosol with the virulent UCD1 strain of feline infectious peritonitis virus (FIPV UCD1) at three different dosage levels. Five of six cats (including sham-vaccinated controls) given the lowest challenge dose showed no signs of disease, while all other cats developed lesions typical of feline infectious peritonitis (FIP). The five surviving cats developed FIP after subsequent challenge with a fivefold higher dose of FIPV. Thus heterotypic vaccination of cats with CCV did not provide effective protection against FIPV challenge.

Animals↗

Evidence for a critical role of diet in the development of insulin-dependent diabetes mellitus.

The role of diet in human insulin-dependent diabetes mellitus (IDDM) has not been properly examined, mainly due to a lack of reliable markers to identify prospective diabetics and the difficulties in obtaining accurate and representative dietary information. Nonetheless, there is some circumstantial evidence suggesting a role for diet in human IDDM. The validity of this relationship in humans must await a sufficiently large, well designed prospective study or the discovery of better markers for diabetes predisposition. The recent availability of the spontaneously diabetic BB rat has permitted prospective studies under controlled conditions which indicate diet, particularly dietary proteins, such as wheat gluten or cow's milk proteins may be prerequisites for maximum expression of the insulin-dependent syndrome in these animals. The early suckling and/or post-weaning period appears to be important and may be the crucial time when these proteins or portions of them pass the gastrointestinal barrier and initiate a process, possibly immunological, which results in destruction of the beta cells of the pancreas.

Animals↗

Immunization against feline coronaviruses.

Feline infectious peritonitis (FIP) is caused by one of several strains of feline coronaviruses which are grouped into 2 general types of viruses. Infection of cats with FIP virus results in production of serum antibodies which may be protective in conjunction with cell mediated immunity, may provided no protection at all, or may produce an immune enhancement to subsequent exposure to another FIP virus or a recrudescence of the original infecting virus. Attempts at immunization of cats against FIP with inactivated or live FIP viruses have been generally unsuccessful, and often sensitizing the cat through immune enhancement rather than providing protection. Heterologous live virus vaccines using viruses of the same antigenic cluster (transmissible gastroenteritis of swine, canine coronavirus, and human coronavirus 229E) have failed to provide protection against FIP virus. Further research into the exact mechanism of protection and immune enhancement is needed in order to understand ways of producing an effective and safe vaccine.

Animals↗

The kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies in cats: calibration to the indirect immunofluorescence assay and computerized standardization of results through normalization to control values.

The computer-assisted, kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies in cats was calibrated to the conventional indirect immunofluorescence assay by linear regression analysis and computerized interpolation (generation of "immunofluorescence assay-equivalent" titers). Procedures were developed for normalization and standardization of kinetics-based enzyme-linked immunosorbent assay results through incorporation of five different control sera of predetermined ("expected") titer in daily runs. When used with such sera and with computer assistance, the kinetics-based enzyme-linked immunosorbent assay minimized both within-run and between-run variability while allowing also for efficient data reduction and statistical analysis and reporting of results.

Animals↗

Response of dairy calves to vaccinia viruses that express foreign genes.

Repeated intradermal inoculations of calves with wild-type vaccinia virus and recombinant vaccinia viruses expressing human hepatitis B virus surface antigen and herpes simplex virus, type 1, glycoprotein D produced characteristic pox lesions at each site of injection. In some instances, calves were inoculated as many as five times at intervals from 4 to 7 weeks. The lesions invariably were more severe after the second inoculation. Subsequent inoculations produced a less severe area of redness, swelling, necrosis, and scab formation. No other signs of illness, such as an elevation in temperature, were noted in the calves. Vaccinia virus was isolated in low titers from scabs taken at various times after inoculation. No lesions were formed at the sites injected with tissue culture fluid and cellular debris at the same time that virus inoculations were made. Calf contact controls remained normal through the 8-week exposure in isolation units with calves inoculated twice with vaccinia virus. No neutralizing antibody to vaccinia virus was detected in the contact controls. In contrast, the virus-inoculated calves developed neutralizing antibody to vaccinia virus and to herpes simplex virus glycoprotein D in serum. In all cattle, a second inoculation significantly enhanced the neutralizing antibody response within 1 week, suggesting that an anamnestic response had occurred. No antibody to hepatitis B virus surface antigen was elicited in calves after repeated inoculations with vaccinia recombinants that express hepatitis B virus surface antigen and are known to elicit in rabbits antibodies reactive with hepatitis B virus surface antigen.

Animals↗

Levels of interferon in blood serum and toxicity studies of bacteria-derived bovine alpha I1 interferon in dairy calves.

This paper reports information on the levels of interferon (IFN) in the blood serum of dairy calves given 10(6) U of bacteria-derived bovine alpha I1 interferon per kg of body weight by intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.), and intranasal (i.n.) routes. Highest levels (10,000 U/ml) in the vesicular stomatitis viral assay system were obtained after i.v. administration and occurred within 30 min of a dose; levels rapidly declined thereafter to a low of 200 to 300 U/ml by 24 h. Serum inhibitory activity against vesicular stomatitis virus in this range is sometimes found in normal dairy calves. Levels after i.m. and s.c. administration were similar: a plateau of 1,000 to 2,000 U/ml between 2 and 8 h after a treatment with a decline to 200 to 300 U/ml by 24 h. Serum IFN was not detected after i.n. dosing or in the control group given physiological buffered saline by the i.m. route. A transitory moderate febrile response, but no other clinical adverse effects, was noted after the first intramuscular dose of IFN, but not after subsequent i.m. doses. No clinical signs were noted after i.v., s.c., or i.n. dosing or in the control calves given physiological buffered saline intramuscularly. After i.v., s.c., and i.m. administration of IFN, leukopenia, neutropenia, and lymphocytopenia were observed; these were most prominent within the first 24 h after the initial dose of IFN.

Administration, Intranasal↗

Effect of dietary vitamin E on the vitamin E status in the BB rat during development and after the onset of diabetes.

Weanling diabetes-prone BB rats were fed AIN-76 diets containing high (HE, 1 g/kg diet), basal (NE, 0.2 g/kg) or low (LE, trace) vitamin E and were killed at 21, 42 or 60 days of age. Plasma and tissues (adrenals, pancreas, spleen, thymus, liver, brown and white adipose tissue, muscle and testes) were analysed for vitamin E. Vitamin E levels reflected the level in the diet and no diabetic animals were detected at these times. In a second experiment, a total of 90 diabetes-prone BB rats were kept on diets LE and HE for 6 months or until they became diabetic. 11/45 on LE and 5/45 on HE became diabetic. Again, plasma and tissue levels of vitamin E reflected the levels in the diet with the exception of the thymus of diabetic rats fed the high vitamin E diet. Thymus vitamin E levels (microgram/g tissue) were 1.8 and 1.2 in LE-fed diabetics and asymptomatic rats, respectively; and 22.7 and 49.5 in HE-fed diabetics and asymptomatic rats, respectively. The last 2 values were significantly different (p less than 0.005). There were no other differences in plasma or tissue levels of vitamin E in these groups of animals. These findings suggest that high dietary vitamin E may decrease the incidence of diabetes in animals which are able to accumulate sufficient amounts of the vitamin in the thymus. Since the thymus plays a key role in the maturation of T cell populations, which appear to be altered in this disease, it seems possible that the protective effect may be exerted at this level.

Adipose Tissue↗

Coronavirus antibody detection in cats by computer-assisted kinetics-based enzyme-linked immunosorbent assay (KELA): field studies.

A total of 2238 feline serum samples submitted to the New York State Diagnostic Laboratory over a 1-year period were tested for the presence of coronavirus antibodies, using the computer-assisted, kinetics-based enzyme-linked immunosorbent assay (KELA). Cats from which sera were obtained were categorized by sex, age, breed, and disease status, and variations in mean antibody titers for different sub-classifications within each category were analyzed by computerized statistical analysis. As expected, higher mean antibody titers were recorded for cats with feline infectious peritonitis, and for cats with a recent history of possible coronavirus exposure. However, an unexpected inverse relationship between coronavirus antibody titer and age was also found. Certain cattery-oriented pure breeds appeared to have higher mean antibody titers, because their sample populations contained a higher percentage of younger cats and cats of unknown age-groups which, over-all, had higher mean titers. Taken together, the data substantiated the efficacy of the computer-assisted KELA for routine detection of serum coronavirus antibodies in cats.

Animals↗

In vitro protective effect of bacteria-derived bovine alpha interferon I1 against selected bovine viruses.

We used bacteria-derived bovine alpha-interferon I1 (Bo IFN-alpha I1) to study its antiviral effect in a bovine turbinate cell line on bovine diarrhea virus, infectious bovine rhinotracheitis virus, parainfluenza 3 virus, and pseudorabies virus. We based our study upon replicate tests for each strain by using a block titration system with various concentrations of Bo IFN-alpha I1 against various concentrations of virus. The data were compiled in two-axis tables (replicate X concentration) and were statistically analyzed by the Spearman-Kärber method. An increase in the concentration of Bo IFN-alpha I1 enhanced its protective effect against every test virus strain. Bo IFN-alpha I1 had a marked in vitro effect on the bovine diarrhea viral strains. It demonstrated less protection against the pseudorabies and parainfluenza 3 viruses. Its effectiveness against the two infectious bovine rhinotracheitis viral strains was lesser and of a low order.

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Diet can prevent diabetes in the BB rat.

When compared with laboratory chow, a defined, semipurified diet prevented diabetes, reduced the frequency of insulitis, increased thymus weight and total white blood cell count, and doubled thymus T-helper/T-suppressor cell ratios in diabetes-prone BB rats. These data show that the diabetic syndrome in BB rats may be prevented or delayed by changes in diet, which may occur through alteration of pathogenic defects in the immune system.

Animals↗

Experimental inoculation of cats with human coronavirus 229E and subsequent challenge with feline infectious peritonitis virus.

Minimal-disease cats exposed to live human coronavirus 229E developed homologous antibody responses that suggested little or no replication of the virus in inoculated animals. Oronasal and subcutaneous inoculation of coronavirus 229E did not elicit an antibody response by heterologous (transmissible gastroenteritis virus, canine coronavirus) neutralization or by heterologous (transmissible gastroenteritis virus) kinetics-based enzyme-linked immunosorbent assay. No clinical signs attributable to coronavirus 229E were seen in inoculated cats. Although the number of animals in each of the five experimental groups was small (n = 2), antibodies produced in response to the virus did not appear to sensitize cats to subsequent feline infectious peritonitis virus challenge, but neither did they cross-protect cats against the challenge dose.

Animals↗

Increased plasma and tissue levels of vitamin E in the spontaneously diabetic BB rat.

Increased plasma and tissue levels of vitamin E were found in spontaneously diabetic BB rats (D) as well as asymptomatic/diabetes-prone BB rats (AD) in comparison to levels in non-diabetic control rats (ND). Treatment of D rats with insulin for 30 days returned plasma and tissue values of vitamin E to control levels. The changes reported here could not be explained solely on the basis of variations in total lipid content of plasma. These data suggest the metabolism of vitamin E is altered in asymptomatic and spontaneously diabetic BB rats and this alteration returns to control values following insulin treatment. Furthermore, it might be speculated that these data indicate a relationship between vitamin E and insulin.

Animals↗

Experimental studies of a coronavirus and coronavirus-like agent in a barrier-maintained feline breeding colony.

Minimal-disease (MD) cats raised in a barrier-maintained feline breeding colony routinely become coronavirus (CV) antibody-positive at 5-8 weeks of age and remain seropositive indefinitely. In addition, they shed coronavirus-like particles (CVLPs) in their feces which are morphologically distinct from "typical" coronaviruses. Oronasal, intraperitoneal, intraduodenal, and intravenous inoculations of CVLPs were uniformly unsuccessful in the seroconversion of cats to CV, whereas subsequent prolonged close contact with colony cats did result in seroconversion. Such evidence indicates that MD cats in this barrier colony are infected with at least two non-crossreactive agents: (1) feline enteric CVLPs, which are shed in feces and are morphologically and antigenically distinct from established coronaviruses (CVs), and (2) a virus which is antigenically cross-reactive with CVs, but which is apparently shed by some route other than the lower gastrointestinal tract.

Animals↗

Serum enzymes in the BB rat before and after onset of the overt diabetic syndrome.

As part of a six-month prospective study of the effects of neonatal thymectomy in the spontaneously diabetic BB Wistar rat, activities of the following enzymes were determined: alkaline phosphatase (AP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and UDP-galactosyltransferase (UDPG). In prediabetics, AP and LDH levels were higher than in sham-operated, non-diabetic controls; however, this increase was seen in nearly all diabetes-prone BB rats, diminishing the usefulness of these changes in discerning potential diabetics from asymptomatic, diabetes-prone rats. After onset of the syndrome, there was a striking elevation of AP values in all diabetics with no similar alteration in asymptomatic, diabetes-prone rats suggesting this was a diabetes-related phenomenon. By contrast, UDPG was the only enzyme to decrease immediately following the onset of the syndrome. Both UDPG and AP levels correlated with blood glucose, the former negatively and the latter positively, suggesting a close relationship with changes occurring after onset of the syndrome. The remaining enzymes increased only in a portion of diabetics alone (GOT, GPT) or in a portion of both diabetics and asymptomatic, diabetes-prone BB rats (LDH, CPK).

Alanine Transaminase↗

Role of recent vaccination in production of false-positive coronavirus antibody titers in cats.

Statistical support was obtained for an association between recent vaccination of cats and the presence of elevated background (i.e., anti-cell culture) reactivity in certain of their sera, as detected with a kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies, implicating routine vaccination as a potential cause of false-positive antibody test results.

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Time course of serum glucoregulatory variables and lipids following neonatal thymectomy of diabetes-prone and control BB Wistar rats fed a defined diet.

The acute diabetic syndrome in the BB Wistar rat resembles human type 1 (insulin-dependent) diabetes, including a possible association with T cell-mediated, (auto)immune processes. In most previous studies 'normoglycemic' littermates of diabetic BB rats have been used as controls and little attention has been paid to the role of diet. It now appears that asymptomatic/diabetes-prone littermates of diabetics have immune system defects as well as metabolic abnormalities. Since there are also indicators that the disease process starts before animals become symptomatic, we looked for prospective metabolic changes in prediabetic, asymptomatic/diabetes-prone and control (diabetes-free) BB rats following intervention in the immune system while maintaining the animals on a defined diet (AIN-76). The results reported here confirm and extend the finding of Like et al. (1982) that neonatal thymectomy reduces the frequency of the syndrome and emphasize the role of diet in modifying its expression. In contrast to previous reports of hyperglucagonemia only after onset of diabetes, asymptomatic/diabetes-prone animals had periodic increases of plasma glucagon values up to 3-fold those of diabetes-free controls; prediabetics displayed a similar pattern. Asymptomatic/diabetes-prone rats also tended to have slightly higher blood cholesterol levels. The low incidence and delayed onset of the syndrome in rats fed a modified AIN-76 diet (27%, 127 +/- 21 days) compared to the previous chow-fed generation (60%, 93 +/- 18 days) and chow-fed littermates (38%, 87 +/- 16 days) suggested that diet can modify expression of the syndrome.

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Experimental inoculation of cats with canine coronavirus and subsequent challenge with feline infectious peritonitis virus.

Oronasal inoculation of minimal-disease cats with a virulent field isolate of canine coronavirus elicited a neutralizing antibody response that increased steadily over a two-month period, indicating in vivo amplification of the inoculated dose. A heterologous neutralizing antibody response to transmissible gastroenteritis virus could be detected three weeks after titers to canine coronavirus were first observed and was found to parallel the homologous response at a level approximately one log10 dilution lower. A modest anamnestic response detectable in both assays was observed after a second exposure to canine coronavirus. Cross-reacting antibodies to transmissible gastroenteritis virus were not detected by a kinetics-based enzyme-linked immunosorbent assay (KELA), however, until after cats had received multiple daily doses of canine coronavirus (third exposure). No clinical signs attributable to canine coronavirus were seen in inoculated cats, and virus could not be isolated from fecal or rectal swabs nor identified in fecal specimens by electron microscopy. Both virus-neutralizing and KELA titers were boosted by aerosol challenge with feline infectious peritonitis virus. Antibodies produced in response to canine coronavirus did not sensitize cats to subsequent feline infectious peritonitis virus challenge, but neither did they protect cats against the challenge dose.

Animals↗