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Biomedical subjects

J R Duncan

Publications and source records attributed to J R Duncan.

At least 19 recordsLinked to original sources

The effect of ascorbic acid on arachidonic acid and prostaglandin E2 metabolism in B16 murine melanoma cells.

Ascorbic acid (Asc), arachidonic acid (AA) and prostaglandin E2 (PGE2) are reported to be important in maintaining the stability of the cell matrix. Asc has also been shown to influence fatty acid (FA) and PGE2 synthesis, with the result that effects of Asc on cell growth are suggested to be mediated through the metabolism of these two compounds. This study examined the effect of Asc, supplemented over the concentration range of 0-100 micrograms/ml, on the in vitro cell growth of non-malignant LLCMK (monkey kidney) cells and malignant B16 murine melanoma cells. The effects of Asc supplementation on AA and PGE2 levels in the cell stroma and membrane fractions of the two cell types was also determined. Asc had no significant inhibitory or stimulatory effect on the growth of either the B16 or LLCMK cells. The total percentage AA composition determined in the B16 control cells (combined stroma and membrane fractions), was similar to that determined in the LLCMK control cells. Asc supplementation of the B16 cells, resulted in an inverse relationship between B16 cell growth and total percentage AA composition. PGE2 concentration in the control B16 cells (combined stroma and membrane fractions) was significantly higher than that detected in the control LLCMK cells. No PGE2 was detected in the B16 stroma fraction, with all appearing to be located in the membrane fraction. However, upon the supplementation of the B16 cells with increasing Asc concentrations, PGE2 appeared to be mobilized from the membrane fraction, resulting in increasing PGE2 levels in the stroma fraction relative to the membrane fraction. This was accompanied by a significant decrease in PGE2 concentration, in the membrane fraction. B16 cell growth and total (stroma and membrane fractions) PGE2 concentration in these cells was inversely related, when cultures were supplemented with increasing levels of Asc. Asc supplementation of the LLCMK cells did not appear to have any significant effect on AA or PGE2 metabolism in these cells.

Animals

Paratuberculosis in saiga antelope (Saiga tatarica) and experimental transmission to domestic sheep.

Mycobacterium paratuberculosis was isolated in low numbers from the small intestine and associated mesenteric lymph nodes of a saiga antelope (Saiga tatarica) using routine culture techniques in spite of histologic evidence of high numbers of acid-fast bacteria in these tissues. Two newborn domestic sheep were fed the ground intestinal tissue containing acid-fast bacteria and the progression of the experimental disease was followed by fecal culture, immunodiffusion (AGID) and lymphocyte stimulation (LST) tests. One experimentally infected sheep developed progressive clinical illness 1 yr postinoculation. Few M. paratuberculosis were isolated from feces or tissues although an extensive granulomatous mycobacterial enteritis, lymphadenitis and lymphangitis were observed containing large numbers of typical acid-fast organisms. No clinical illness was observed in the second inoculated sheep after 18 mo of observation, although infection was demonstrated at necropsy. Both sheep developed AGID and LST reactions indicative of paratuberculosis. This study demonstrated that a difficult to culture isolate of M. paratuberculosis was responsible for paratuberculosis in captive wild ruminants and was transmissible to domestic sheep. Diagnosis of paratuberculosis in four of eight of the imported saiga antelope and in eleven of their 18 offspring indicates the importance of this disease in management of captive wild ruminants and the ease with which this organism can be transmitted.

Animals

Effects of phosphorus/calcium-restricted and phosphorus/calcium-replete 32% protein diets in dogs with chronic renal failure.

Twenty-four dogs with induced, severe chronic renal failure were allotted to 2 groups of 12 each. Group-A dogs were fed a 0.4% phosphorus (P)/0.6% calcium, 32% protein diet, and group-B dogs were fed a 1.4% P/1.9% calcium, 32% protein diet. Dogs were studied over 24 months to determine clinical status, survival, blood biochemical alterations, glomerular filtration rate (GFR), urinary excretion of P and protein, renal morphologic changes, and renal tissue concentrations of calcium, P, and magnesium. Group-A dogs developed statistically significant differences from group-B dogs in several blood biochemical values (PCV and total solids, calcium, P, potassium, sodium, chloride, total CO2 (TCO2), anion gap, and parathyroid hormone concentrations) and in urinary P excretion. Mean (+/- SEM) GFR values in group-A and group-B dogs were nearly identical when diets were initiated (group A = 0.73 +/- 0.05 ml/min/kg of body weight; group B = 0.72 +/- 0.08 ml/min/kg), but significantly (P = 0.0346) lower GFR developed in group-B than in group-A dogs over time. At 24 months, GFR in survivors was 0.83 +/- 0.08 and 0.63 +/- 0.15 ml/min/kg for dogs of groups A and B, respectively. Other measurements favored the hypothesis that P/calcium restriction was beneficial, but values failed to reach statistical significance. Survival was greater at 24 months in group-A than in group-B (7 vs 5) dogs, and renal tissue concentrations of calcium and P were higher in group-B than in group-A dogs. Differences were not detected between groups in urinary excretion of protein and in the type or severity of renal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

Possible involvement of delta-6-desaturase in control of melanoma growth by gamma-linolenic acid.

This study examined the effects of linoleic acid (LA) and gamma-linolenic acid (GLA) on BL6 melanoma growth in cell culture and of safflower oil (SFO) which contains LA and evening primrose oil (EPO) which contains GLA, on melanoma growth when grown in mice. The delta-6-desaturase activity of the melanoma cells in the two systems was also examined and an attempt made to relate the activity of the enzyme to the effects of GLA on cell and tumour growth. LA and GLA were found to be equipotent in inhibiting growth of the in vitro cultured BL6 cells which were found to contain an appreciable level of delta-6-desaturase activity. EPO was however found to be a more potent promoter of in vivo melanoma growth in mice than SFO. Melanomas grown in mice were found to lack delta-6-desaturase activity suggesting that the EPO diet, by providing GLA, was able to compensate for the loss of enzyme activity in the melanomas. The possibility that melanomas in mice have a requirement for GLA for growth while in in vitro cultured cells excess GLA inhibits the growth of the cells through an increase in lipid peroxidation is discussed.

Animals

Serological response of the bovine fetus to bovine viral diarrhea virus.

Susceptible pregnant heifers were inoculated with bovine viral diarrhea virus at 150 days of gestation and earlier. Fetuses were surgically collected at selected times after inoculation. Serum immunoglobulins were quantitated, and the presence of specific antibodies was determined. In fetuses from heifers inoculated at 150 days, immunoglobulin M (IgM) appeared approximately 2 weeks after inoculation and was followed in 7 days by IgG1. Later IgG2 was detected in the sera of three fetuses. Serum-neutralizing and complement-fixing antibodies were first detected in a fetus taken at 206 days of gestation. Fetuses taken at later times also had specific serum antibodies. Possible explanations for the appearance of serum immunoglobulin substantially before specific bovine viral diarrhea antibodies include the viral alteration of host tissues rendering them antigenic viral activation of polyclonal B cells, and viral modulation of virus-specific lymphocytes causing specific interference with the appearance of antiviral antibodies. In one of the fetuses having IgG2, the serum also contained IgA. Placental leakage of material immunoglobulins was thought to be responsible for the presence of IgA and IgG2 in this fetus. Small quantities of IgM were found in the serum of two fetuses taken from heifers inoculated between 65 and 95 days of gestation, but specific antibodies were found in none.

Animals

Cytology of canine cutaneous round cell tumors. Mast cell tumor, histiocytoma, lymphosarcoma and transmissible venereal tumor.

Sixty-four canine cutaneous round cell tumors were divided into 25 mast cell tumors, 15 histiocytomas, nine cutaneous lymphosarcomas and 15 transmissible venereal tumors. The final diagnosis was made from cytologic, clinical and histologic findings. Cytologic features were significantly distinctive in mast cell tumor, transmissible venereal tumor, and most cases of histiocytoma and lymphosarcoma to allow a diagnostic opinion. This opinion was supported by subsequent histologic examination. In some instances cytology was considered essential in rendering a diagnostic opinion even though histology was available.

Animals

Bovine fetal inoculations with calf rotavirus.

The serological and histopathological responses of bovine fetuses to in utero inoculation with virulent and attenuated strains of the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) are described. Thirteen bovine fetuses, 63 to 190 days of gestation, were inoculated in utero with attenuated (three fetuses) or field strain virus (nine fetuses) or both (one fetus).Serum-neutralizing antibody titers ranging from 1:16 to > 1:256 were detected in six of eight fetuses tested, demonstrating the ability of the bovine fetus to respond immunologically to this agent. The youngest fetus in the series was inoculated at 63 days of gestation and developed a titer of 128 in 64 days. This represents the earliest stage of gestation at which a bovine fetus has been inoculated with a bovine virus and found to produce antibody to it. Serum neutralizing titers in six of the eight dams tested increased significantly following the inoculations of their fetuses in utero. Histological changes associated with viral replication and antigenic stimulation of the lymphoreticular system were observed. Pneumonic lesions consisting of both local and diffuse lymphoreticular proliferation were present in five of the nine fetuses that were alive at slaughter. Gliosis and perivascular cuffing were noted in the brains of two of these fetuses and meningitis was seen in one. No evidence of teratogenic change was found.

Animals

Age and milk production data of cattle culled from a dairy herd with paratuberculosis.

Statistical assessment of age and milk production data revealed a significantly shorter life expectancy and reduced milk production of Mycobacterium paratuberculosis-infected dairy cows, when compared with non-infected herdmates. High producing cows were frequently culled after their 1st or 2nd gestation, contributing to an undetermined economic loss with regard to their potential breeding value. Cows with subclinical infection frequently had problems of infertility and of mastitis.

Age Factors

An interaction between zinc and vitamin A in pregnant and fetal rats.

A possible interaction between zinc and vitamin A metabolism was studied in pregnant rats. Rats were depleted of vitamin A by feeding retinoic acid during growth. At mating, they were fed diets containing 100, 9, or 0.5 microgram/g zinc and were given orally 400, 8, or 0 microgram/kg body weight/day of retinyl palmitate. Low intake of zinc, but not of vitamin A, caused maternal body weight gain, placental weight, and fetal weight all to be low. The number of implantation sites affected and the proportion of fetuses malformed were dependent on intake of both zinc and vitamin A, and there was a significant interaction between these nutrients in regard to both of these parameters. In maternal as well as in fetal animals, plasma and liver zinc concentrations were low in groups fed low levels of zinc, but not in those given low vitamin A. Liver vitamin A values were affected by vitamin A intake but not by dietary zinc concentration. However, plasma vitamin A concentration in both maternal and fetal animals was significantly reduced by low intake of either zinc or vitamin A. There was a significant interaction between these two nutrients in regard to plasma vitamin A. These data indicate an interaction between zinc and vitamin A metabolism possibly at the level of vitamin A mobilization from the liver.

Abnormalities, Drug-Induced

Intestinal absorption of zinc: a role for a zinc-binding ligand in milk.

This study examined the proposal that a low molecular weight, zinc-binding ligand (ZBL) in certain milks is important for zinc absorption in the neonatal period. Ten-day-old rats, in which intestinal ZBL is absent, fed (by stomach intubation) 65Zn-labeled ZBL from rat milk, absorbed significantly more 65Zn than those fed free 65ZnCl2 or bovine milk fractions. ZBL from human milk appeared to have an intermediate effect, possibly due to species specificity. 65Zn was found in the ZBL fraction in intestinal mucosa of 10-day-old rats fed rat or human milk fractions, but not in those fed bovine milk or free 65ZnCl2. In contrast, in 18-day-old rats, which have an endogenous intestinal ZBL, there were no differences in zinc absorption, and any of the labeled milk fractions or free 65Zn caused localization of 65Zn in the ZBL fraction of intestinal mucosa. These results support the hypothesis that the intestinal ZBL plays a role in zinc absorption and that in the neonatal period before its development the milk ZBL is valuable for this function. This mechanism may be important in normal human infants as well as in acrodermatitis enteropathica patients.

Acrodermatitis

Pathological evaluation of paratuberculosis in naturally infected cattle.

Thirty-two of 51 cattle infected with Mycobacterium paratuberculosis had chronic enteritis, chronic lymphangitis or mesenteric lymphadenopathy, or all three, at slaughter. Granulomatous inflammatory lesions were mild to advanced and predominantly involved the distal small intestine. Rectal involvement was seen only in five cattle. Fourteen had microgranulomas in the liver. There were three cytological forms of macrophages: histiocytic, polygonal and epithelioid. The latter two types had engulfed moderate numbers of acid-fast bacilli. The histiocytic macrophages usually were packed with acid-fast bacilli. Except in the liver and occasionally its nodes, remote lesions of paratuberculosis were not found in other organs. One animal had endocardial and aortic calcifications. Most cattle with signs of diarrhea had globule leukocytes in or around myenteric ganglion cells. The thymus of 3- to 8-year-old cattle with clinical signs frequently had mild to advanced involution. The thymus of similarly aged infected animals without clinical signs, and of paratuberculosis-negative animals, had not involuted.

Animals

Feline panleukopenia. III. Development of lesions in the lymphoid tissues.

Germfree and specific pathogen-free cats were inoculated with feline panleukopenia virus. Cats were necropsied 2 to 6 days after inoculation and tissues from the thymus, lymph nodes and spleen taken for histological and immunofluorescence studies. Necrosis of lymphoid cells in the thymic cortex began 3 days after inoculation and continued for 5 to 6 days after inoculation when the thymus was nearly depleted of lymphocytes. Immunofluorescence studies showed the lesions to be caused by virus. There was gross and histological involution of the thymus in both germfree and specific pathogen-free cats. The lymph nodes and spleen of uninoculated germfree cats looked "inactive" and lacked well developed lymphoid follicles and paracortical areas. In both germfree and specific pathogen-free cats there was necrosis in both follicular and paracortical areas of the lymph nodes and follicular and periarteriolar areas of the spleen 3 to 4 days after inoculation. Immunofluorescence showed these areas had virus infection. By 5 to 6 days after inoculation, these areas were populated by many lymphoblastoic cells. Even though significant destruction of lymphoid cells occurred, subsequently, in cats that develop mild clinical illness, these lymphoid tissues seemed stimulated rather than depleted of lymphocytes.

Animals

In vitro lymphocyte transformation as a herd survey method for bovine paratuberculosis.

The lymphocyte-transformation (LT) test was evaluated for its potential application as a field test for bovine paratuberculosis. Using a whole blood technique, samples from 3 consecutive collection periods were subjected to 3 mycobacterial antigens and to phytohemagglutinin. The results obtained from LT were compared with conventional serologic and cultural methods. A positive LT response to johnin purified-protein derivative (PPD) or avian PPD (or both) was noted in 40% to 60% of the animals tested. The complement-fixation test yielded 4% to 6.7% positive results, the immunodiffusion test between 1.2% and 1.4%, and the direct fecal culture between 2.4% and 6%. The mean of the stimulation indices of all positively responding animals was highest with johnin PPD. Specific stimulation to mammalian PPD occurred between 2.4% and 6% of the animals. The efficacy of the LT test for determining the incidence of infection with Mycobacterium paratuberculosis is discussed.

Animals

Johne's disease and the practitioner.

Mycobacterium paratuberculosis infections and the disease states resulting in cattle are defined as spectral in nature. There is a spectrum of immunological response which complicates tests based on this. It is recommended that initial diagnosis of suspicious clinical cases be confirmed by direct fecal smears and a serological test such as immunodiffusion. Herd evaluation requires the application of fecal cultures plus immunodiffusion. Control requires rigid management hygiene measures, surveillance of the herd status and post mortem confirmation of salvaged animals.

Animals