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Biomedical subjects

R M Phillips

Publications and source records attributed to R M Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1990

Chlamydial infection and perinatal mortality in a swine herd.

Chlamydia psittaci was believed responsible for an episode of high perinatal death loss in a swine herd in which 8.5 pigs per litter normally were weaned. In this episode, 18 sows produced 186 pigs, with 50 survivors. Chlamydia was found in tissue samples, and other bacterial or viral pathogens could not be identified. Chlamydia was diagnosed by isolation (ELISA), histologic examination using immunoperoxidase staining techniques, and electron microscopy. Previously, C psittaci has not been considered in the differential diagnosis of swine perinatal mortality.

Animals↗
PubMed1989

Influence of site on the chemosensitivity of transplantable murine colon tumours to flavone acetic acid (LM975, NSC 347512).

A number of experimental studies have demonstrated significant responses of s.c. solid tumours to flavone acetic acid (FAA). Clinical studies to date have been disappointing, with no objective responses being seen. The present study demonstrated that the tumour site is important for the anti-tumour action of FAA against two transplantable adenocarcinoma lines (MAC) in NMRI mice. Responses were achievable only when the tumours were implanted s.c. Ascitic or systemic tumours did not respond to FAA. Experimentally achievable plasma levels of FAA were not sufficient to induce significant cell kills in either MAC 15A or MAC 26 cell lines in vitro. A poor correlation exists between in vitro and in vivo responses, as the clonogenic assay could not predict the response of the solid MAC tumours grown s.c. The in vitro data indicated that the length of exposure to FAA was important, with long exposure times being necessary for cytotoxicity to develop, in these tumour cell lines. These studies imply that more than one mechanism is involved, and it is likely that the activity of FAA against s.c. tumours relies at least in part on a specific biological feature of tumours in this site. However, it may still be possible to achieve systemic tumour cell kill in vivo by increasing drug-exposure times.

Adenocarcinoma↗
PubMed1988

Experimental correlations of in vitro drug sensitivity with in vivo responses to ThioTEPA in a panel of murine colon tumours.

Cell lines derived from three histologically different murine colon tumours (MAC) were used to assess whether or not a tumour colony-forming assay could have retrospectively predicted the wide range of in vivo responses to the alkylating agent, ThioTEPA. Tumour responses ranged from sensitive (MAC 26) to resistant (MAC 15A), with MAC 13 showing only moderate sensitivity. In vitro chemosensitivity studies, in conjunction with pharmacokinetic data, suggest that plasma levels of the drug's primary metabolite, TEPA, should be sufficient to induce significant cell kills in all three tumour lines in vivo. Preliminary studies on the effect of pH on the cytotoxic properties of ThioTEPA in vitro have demonstrated an improved cell kill when cells were exposed to the drug under acidic conditions. As these tumours differ histologically in terms of vascularisation, tumoural pH may play an important part in determining drug efficacy and go some way towards explaining the poor in vitro/in vivo correlation in this model.

Adenocarcinoma↗
PubMed1988

In vitro and in vivo responses of a panel of murine colon tumours to TCNU: a positive correlation.

TCNU is highly active against a panel of three histologically distinct transplantable murine adenocarcinomas of the colon (MAC tumours). Significant reductions in colony formation (greater than 70%) were observed in vitro in all three cell lines following a 1 h exposure to TCNU at experimentally achievable drug C X t values. A good correlation exists between in vivo tumour responses and in vitro cell responses in all cases. Dose-response curves generated at increasing exposure times suggest that no active or long lived products of TCNU are formed as a result of the drug's spontaneous breakdown in vitro (rate of breakdown was 0.078 micrograms min-1 at 37 degrees C). Preliminary studies with the HT-29 human colon cell line have demonstrated that multi-cellular spheroids are more responsive to TCNU (2 X) than the same cells cultured as monolayers.

Animals↗
PubMed1988

Fluctuating ambient temperature for weaned pigs: effects on performance and immunological and endocrinological functions.

Following weaning at 3 wk of age, crossbred barrows and gilts were housed in temperature-controlled rooms for a 5-d adjustment period at 35 degrees C, then assigned to receive constant ambient temperature (CT) or fluctuating ambient temperature (FT) treatment for the nursery phase of the experiment. Pigs in FT received 12 h at 35 degrees C and 12 h at 15 degrees C daily for the initial 2 wk of the experiment, then 12 h at 29 degrees C and 12 h at 9 degrees C daily for the final 2 wk. Pigs in CT received 35 degrees C and 29 degrees C continuously for the first and final 2 wk, respectively. Weekly growth performance, feed intake and feed-conversion efficiency were not affected by treatment. Plasma glucose, serum cortisol, monocyte phagocytic function and antibody response to a commercial E. coli bacterin were similar in pigs exposed to CT and FT treatments. Concentrations of insulin in serum were similar between treatments at 0, 1 and 3 wk but were increased for pigs in FT at 2 (P less than .05) and 4 wk (P less than .01). Numbers of lymphocytes, band neutrophils and monocytes in pigs were not influenced by ambient temperature treatment. However, numbers of mature neutrophils for pigs in FT were increased (P less than .05) at 1 and 3 wk of treatment. Eosinophils were also elevated in FT pigs at 4 wk of treatment. Pairs of littermate pigs that had been given CT and FT treatments were selected randomly to continue on the finishing phase of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1988

Enzyme-linked immunosorbent assay for canine serum ferritin, using monoclonal anti-canine ferritin immunoglobulin G.

Immunoassay of serum ferritin is currently used to evaluate the clinical iron status of human beings, horses, cattle, and swine. Because ferritins are immunologically species specific, a separate assay must be developed for each species. We have developed an ELISA for serum ferritin in dogs, using a monoclonal anti-canine ferritin antibody. Ferritin standards were linear (r = 0.997) from 0 to 80 ng/ml. Recovery of ferritin from canine serum was 94%. Dilutions of pooled canine serum were linear from 0 to 50% (r = 0.994). Within-assay coefficient of variability was 5.5%, whereas assay-to-assay coefficient of variability ranged from 12.5 to 21%. This assay should provide a nonsurgical means of accurately estimating dogs' iron stores.

Animals↗
PubMed1987

Influence of the tissue distribution of ThioTEPA and its metabolite, TEPA, on the response of murine colon tumours.

Disposition studies in the same animals as those used for assessment of antitumor and toxic effects could increase understanding of the variation in response to cytotoxic drugs. Tissue and plasma levels of ThioTEPA and triethylenephosphoramide (TEPA) were measured to see if any correlation existed between them and the effects of the drug on a series of mouse colon tumours (MAC). The tumour panel included an ascitic form (MAC 15A), an anaplastic (MAC 13) and a well-differentiated (MAC 26) solid tumour, all grown subcutaneously. The maximum tolerated dose of ThioTEPA was 20 mg kg-1 in females bearing MAC 13 and 15 mg kg-1 in males having MAC 15A or 26. The diverse growth characteristics of the tumour cell lines necessitated the use of different methods for assessment of response. After administration of the maximum tolerated dose, the greatest response was observed in MAC 26, in which a growth delay of 15 days-twice the doubling time of the tumour volume-occurred. ThioTEPA produced 58% inhibition of MAC 13 tumour weight, but MAC 15A was unresponsive. One hour after intraperitoneal administration of Thio-TEPA (20 mg kg-1), ratios of tissue to plasma concentration were 1.13, 0.87 and 1.17 in tumours and 0.80, 0.75 and 0.73 in spleens of mice bearing MAC 13, 15A and 26 respectively. These data show greater accumulation of drug in neoplastic than in normal tissues. The pattern of distribution of the metabolite was similar, but there was a lesser degree of tissue accumulation than by the drug. Concentrations of drug and metabolite in neoplastic tissues related to their protein content were 116.0, 126.3 and 183.3 micrograms ThioTEPA/g and 57.5, 83.1 and 78.6 micrograms TEPA/g in MAC 13, 15A and 26 respectively. Combination of these chemosensitivity and pharmacokinetic data indicates that differences in response of these tumours to ThioTEPA cannot be explained by the availability of the drug and metabolite. The therapeutic effects of ThioTEPA cannot be predicted purely from a knowledge of drug and metabolite disposition.

Adenocarcinoma↗
PubMed1987

Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid).

LM985 has been shown previously to hydrolyse to flavone acetic acid (LM975) in mouse plasma and to produce significant anti-tumour effects in transplantable mouse colon tumours (MAC). It has undergone Phase I clinical trials and dose limiting toxicity was acute reversible hypotension. Substantially higher doses of LM975 can be given clinically without dose limiting toxicity. We have investigated the activity of LM975 against a panel of MAC tumours and also the in vitro cytotoxicity of both LM985 and LM975 in two cell lines derived from MAC tumours. LM985 is considerably more cytotoxic than LM975 in vitro but increased length of exposure to LM975 results in improved activity. Single in vivo injection of LM975 showed no activity against the ascitic tumour MAC 15A, moderate activity against the s.c. poorly differentiated tumour MAC 13 and produced a significant growth delay in the well differentiated MAC 26. These latter responses were considerably enhanced by repeated injection 7 days later. Pharmacokinetic studies in mice following i.p. injection of LM985 demonstrated rapid degradation of LM985 to LM975 in the peritoneum. Length of exposure as well as drug concentration appear important factors in determining anti-tumour responses.

Adenocarcinoma↗
PubMed1986

Virus isolation from semen of bulls serologically positive for bluetongue virus.

Isolation of bluetongue virus was attempted from 85 semen samples taken from 3 long-term seropositive bulls and 9 short-term seropositive bulls in an artificial breeding service unit. Two types of cell cultures susceptible to bluetongue virus were used for virus isolation. Extended sonication, centrifugation of specimens, and treatment of cell cultures with dimethyl sulfoxide and diethylaminoethyl-dextran were used to enhance virus attachment and infection of cell cultures. Virus isolation results were negative on all specimens. These results indicate that at the limits of the methods used, bluetongue virus-seropositive bulls do not have long-term latent bluetongue virus in their semen.

Animals↗
PubMed1985

DR antigens in systemic sclerosis: lack of clinical correlations.

The information available in the literature is controversial as to the association between HLA-DR and systemic sclerosis (SS). We studied 44 Caucasians with SS and found DR1 (P = 0.025; RR = 2.4) and DR5 (P = 0.05; RR = 3.8) to be increased whereas DR3 was not found to be increased when compared to local controls. The possible influence of a DR specificity in the clinical manifestations of SS was also investigated but not found.

Gene Frequency↗
PubMed1983

Use of enzyme-linked immunosorbent assay for detection of K88 pili in fecal specimens from swine.

Enterotoxigenic Escherichia coli are important in neonatal pig diarrhea. To be pathogenic, E coli must possess the ability to produce toxin and adherence structures called pili. An enzyme-linked immunosorbent assay was used to detect K88 pili in feces of swine. Results were compared with standard isolation and identification techniques. Isolates were tested for labile toxin production by the Y-1 mouse adrenal gland test and presence of pili by the enzyme-linked immunosorbent assay test. The ability to detect K88 pili in feces correlated with the isolation of labile toxin-positive, K88-positive E coli.

Animals↗
PubMed1982

Using enzyme-linked immunosorbent assay to detect Escherichia coli K88 pili antigens from clinical isolates.

Colonization of the small intestine is a prerequisite for enterotoxigenic Escherichia coli (ETEC) to cause diarrheal disease. Colonization is dependent on the capability of ETEC to adhere to the villous epithelium of the small intestine. This adherence attribute is conferred by pili structures produced by ETEC. The present study compares the efficiencies of the standard agglutination test, Y-1 mouse adrenal cell test, and infant-mouse gastric test with the efficiency of the enzyme-linked immunosorbent assay (ELISA) for the detection of the K88 pilus antigen and enterotoxin-producing E coli. The ELISA, a double antibody sandwich assay utilizing specific anti-K88 pilus antiserum, was used. Identification of isolates from clinical samples was accomplished on suspensions of bacteria. The sensitivity of the assay was in the nanogram per milliliter range, as determined by measuring purified pili. Results could be determined visually, but quantitative results indicated a positive optical density to negative optical density rate of 1.9 to greater than or equal to 3.0 on samples submitted to a clinical laboratory. The development of this assay indicates the application of such an ELISA for rapid identification of ETEC possessing K88 pili.

Agglutination Tests↗
PubMed1981

Abnormal responses of granulocytes in chronic granulomatous disease.

Stimulation of normal granulocytes with chemotactic factor, phorbol myristate acetate, concanavalin A, and calcium ionophore results in rapid depolarization which precedes the 'respiratory burst'. Treatment of granulocytes in chronic granulomatous disease with these stimulants fails to generate chemiluminescence. This defect is associated with an absence of transmembrane potential shifts in response to treatment with chemotactic factor, phorbol myristate acetate, and concanavalin A while depolarization in response to A23187 is unaffected by this disease state.

Calcimycin↗