Search PubMed⌕ Search

Biomedical subjects

A M Craig

Publications and source records attributed to A M Craig.

At least 91 records · Page 5Linked to original sources
PubMed1991

Evaluation of the oral vitamin E absorption test in horses.

An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol. Absorption of the 2 doses of dl-alpha-tocopherol acetate indicated a dose response; the area under the curve at 24 hours (AUC24) was 4.3 micrograms.h/ml for the 45-IU/kg dose and 32.2 micrograms.h/ml (P less than 0.01) for the 90-IU/kg dose. Maximal absorption was apparent when vitamin E was naturally consumed in grain, compared with administration of identical preparations by stomach tube or paste. In the same horses, dl-alpha-tocopherol and dl-alpha-tocopherol acetate plus polyethylene glycol had statistically similar absorption curves and both had significantly greater AUC24, compared with dl-alpha-tocopherol acetate; values for the 3 compounds were 23.6, 25.8, and 12.6 micrograms.h/ml, respectively. The AUC24 varied between individual horses, but time of peak value was consistently observed between 6 and 9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Secreted phosphoprotein mRNA is induced during multi-stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts.

Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44-kDa bone phosphoprotein, bone sialoprotein I, and transformation-related phosphoprotein, is a 41.5-kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate-to-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In a set of 5 independently isolated T24-H-ras-transfected mouse C3H 10T1/2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from B16F1 melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.

Animals↗
PubMed1990

Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression.

Secreted phosphoprotein 1 (Spp-1; osteopontin) is one of the abundant noncollagenous proteins in bone matrix and is produced by osteoblasts. We examined the promoter region of the mouse Spp-1 gene and identified a sequence responsible for 1,25-dihydroxyvitamin D3 enhancement of the Spp-1 gene expression. This 24-base-pair (bp) sequence (vitamin D response element) is located 761 bp upstream of the transcription start site and consists of two direct repeats of a unique 9-bp motif, AGGTTCACG. The vitamin D response element confers responsiveness of a heterologous promoter to 1,25-dihydroxyvitamin D3 in a position- and orientation-independent and copy-number-dependent manner. The basal level of expression of the reporter constructs containing this sequence and its response to 1,25-dihydroxyvitamin D3 were not affected by cotreatment with transforming growth factor beta or the tumor promoter phorbol 12-myristate 13-acetate or by cotransfection with a JUN expression vector. The vitamin D response element forms DNA-protein complexes, as indicated by gel-retardation assays. The addition of a monoclonal antibody raised against the vitamin D receptor further retarded the mobility of the DNA-protein complex. Another antibody that recognizes the DNA binding region of the vitamin D receptor attenuated its binding to the sequence. These results indicate that this 24-bp sequence containing two 9-bp motifs binds to the vitamin D receptor and mediates the vitamin D3 enhancement of murine Spp-1 gene expression.

Animals↗
PubMed1990

Expression of attachment proteins during cementogenesis.

There is general agreement that during development the extracellular environment plays a critical role in controlling cell differentiation. Data generated from numerous studies support the possibility that cell attachment proteins and their corresponding cell receptors are possible candidates for this role. In particular, our studies are directed at identifying attachment proteins in mature cementum and establishing the function of these proteins during root formation. Fractionation of guanidine HCL/EDTA extracts of cementum revealed the presence of a bone-associated attachment, BSP, as well as fractions containing as of yet undetermined attachment proteins. Immunofluorescent examination of 1st molar tissues during root formation, obtained from 7 day-old mice neonates, for bone-associated attachment proteins indicated that osteopontin is expressed in the area of Hertwig's epithelial root sheath, but not in the region of the dental papillae. However, dental papillae cells, considered to have the capacity to form cementum, attached to osteopontin coated dishes, in vitro. Thus, unique attachment proteins, as well as those previously identified, were found in mature cementum and during root development. Future studies focused on identifying attachment proteins of mature cementum and determining the spatial and temporal localization of these proteins, pre- and post-cementogenesis, will provide important information necessary for establishing the function of these proteins during root development.

Animals↗
PubMed1990

Identification of a serum-inducible messenger RNA (5B10) as the mouse homologue of calcyclin: tissue distribution and expression in metastatic, ras-transformed NIH 3T3 cells.

A mouse mRNA, provisionally designated 5B10, has been cloned based on its inducibility by serum in quiescent murine fibroblasts. Here we report the full-length complementary DNA sequence and a partial characterization. There are about five copies of the gene in the mouse genome. Sequence analysis of the 5B10 coding region reveals 94 and 97% amino acid identity to human and rat calcyclin, respectively. Although the coding region has been highly conserved during evolution of the rodent and human genomes, the untranslated flanking sequences differ significantly. A protein of Mr about 8000 was produced by in vitro translation of the mRNA transcribed in vitro from 5B10 complementary DNA in a riboprobe vector. An antiserum raised against a portion of the predicted human calcyclin protein cross-reacted with this mouse protein. 5B10 mRNA was found in greatest amount in organs containing proliferating cells, e.g., epidermis, skin, stomach, uterus of pregnant mouse, placenta, and decidua. Brain, liver, mature thymus, and skeletal muscle had little or no detectable 5B10 mRNA. 5B10 mRNA levels were higher in cells treated with 7,12-dimethylbenzanthracene and 12-O-tetradecanoylphorbol-13-acetate than in their normal counterparts, suggesting a role in tumorigenesis. In addition, high 5B10 mRNA levels were associated with metastatic ability in a series of ras-transformed cells, in proportion to levels of ras p21 expressed by the cells, implicating 5B10 even more deeply in carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis.

A murine mRNA (provisionally called 2ar) is described whose abundance is greatly increased by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate both in JB6 epidermal cells in vitro and in epidermis in vivo. We have previously shown induction of 2ar in epidermal or fibroblast cell lines by tumor promoters, growth factors, and transformation with H-ras. The 2ar mRNA appears to be derived from a single copy gene. It encodes the mouse homolog of rat osteopontin, a 41.5-kDa glycosylated bone phosphoprotein that binds to fibroblasts and osteosarcoma cells and to hydroxylapatite (bone matrix). The rat and mouse sequences are 84% identical at the amino acid level and 87% identical at the nucleotide level. Many of the primary structural features are conserved, including a run of 9-10 aspartic residues and a Gly-Arg-Gly-Asp-Ser cell adhesion sequence. Antiserum raised against portions of the predicted polypeptide immunoprecipitated proteins of apparent Mr 55,000-70,000 both from reticulocyte lysates containing the translation products of hybrid-selected mRNA and from cell culture medium containing metabolically labeled proteins secreted by JB6 cells. The results presented here demonstrate that osteopontin is identical to a transformation-associated phosphoprotein whose level of expression by cultured cells and abundance in human sera has been correlated with tumorigenicity. These results suggest a role for osteopontin in carcinogenesis. The murine version of osteopontin has been given the formal name "secreted phosphoprotein 1" and the designation spp.

Amino Acid Sequence↗
PubMed1989

Variations of serum vitamin E, cholesterol, and total serum lipid concentrations in horses during a 72-hour period.

Fluctuations of serum vitamin E (alpha-tocopherol), cholesterol, and total lipids were monitored in 12 horses at 3-hour intervals for 72 hours. Mean coefficients of variation were 12, 5, and 15%, respectively. Statistical analyses were used to conclude that instrumentation error was accountable for only a small portion of the vitamin E variation. Results indicated that a single serum sample assay is an unsatisfactory indicator of vitamin E status in horses. These data have clinical application in the evaluation of horses suspected to be affected with equine degenerative myeloencephalopathy. The large variance of serum total lipids and the lack of correlation of it with serum vitamin E over time preclude the use of vitamin E/serum total lipids ratio in assessing vitamin E status.

Animals↗
PubMed1988

Identification of the major phosphoprotein secreted by many rodent cell lines as 2ar/osteopontin: enhanced expression in H-ras-transformed 3T3 cells.

/ar, a tumor promoter-inducible protein secreted by mouse JB6 epidermal cells, is the murine homolog of rat osteopontin, or 44 kD bone phosphoprotein. We report here that 2ar is also related to pp69, a major phosphoprotein secreted by normal rat kidney cells. Antisera raised against pp69 and against beta-galactosidase-2ar fusion proteins are able to immunoprecipitate the same major phosphoproteins, of apparent Mr 55-69 kD, secreted by several rat and mouse cell lines. The levels of secreted protein and cytoplasmic mRNA are dramatically elevated in NIH 3T3 cells transformed with the human bladder cancer T24 (H-ras) oncogene. These results and the work of Senger and colleagues (Cancer Res., 45, 5818-5823, 1985) imply that enhanced secretion of 2ar/pp69/osteopontin by transformation of a wide variety of mammalian fibroblasts and epithelial cells is often correlated with tumorigenicity.

Animals↗
PubMed1987

Evaluation of the potential for interference by dimethyl sulfoxide (DMSO) in drug detection in racing animals.

Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfere with the detection of these drugs.

Acepromazine↗
PubMed1986

Suspected chlorpyrifos toxicosis in a llama, and plasma pseudocholinesterase activity in llamas given chlorpyrifos.

Five days after treatment with chlorpyrifos, a 1.5-year-old male llama was unable to stand, had saliva flowing from its mouth, and had constricted pupils, hyperglycemia, a metabolic acidosis, and a plasma pseudocholinesterase activity of 111 IU/L. Mean (+/- 1 SD) plasma pseudocholinesterase activity of 29 healthy llamas was 233.76 +/- 51.55 IU/L. Five to 8 days after topical application of chlorpyrifos (25 mg/kg of body weight) to 3 healthy llamas, the pseudocholinesterase activity decreased to 38% to 62% of pretreatment (base-line) activity and returned to within 90% of base-line activity by the 36th to 48th day after treatment.

Animals↗
PubMed1986

Effects of racing on hematologic and serum biochemical values in greyhounds.

Blood samples were collected on nonracing days from 57 racing Greyhounds at 2 weeks, 8 weeks, 13 weeks, and 16 weeks after the beginning of the racing season. Hematologic and biochemical tests were performed to detect marked changes induced by stress of racing. In general, these Greyhounds were healthy. Rhabdomyolysis was detected in one dog. In several other dogs, possible subclinical muscle injury was identified by increased serum creatine kinase activities. Mean serum Ca concentrations tended to decrease during the racing season. None of the tests was a good predictor of racing performance. Mean values for several hematologic and biochemical tests were different from those of other breeds of dogs.

Animals↗
PubMed1986

A chronic in vivo liver perfusion technique in ruminants.

A model for chronic perfusion of the liver of ruminants was developed. This allowed for investigation of the pathophysiology of pyrrolizidine alkaloids (PA) in two species. This model has general application to toxicological studies for both acute or chronic perfusion, as well as, metabolic studies utilizing sheep, cattle or goats. Catheterization of the portal vein via the right ruminal vein was done to separate the ruminal effects of toxin metabolism and absorption from the direct effects of PA on liver tissue. The selection of this vessel insured the equal distribution of infused substances throughout all lobes of the liver. A left flank laparotomy surgical approach was used. A dacron patch glued to the catheter at vein entry site eliminated a number of common catheter problems. Catheters were used for infusion of up to 2 L/daily for 20 d to 7 mo.

Animals↗
PubMed1986

Pharmacokinetic disposition of dimethyl sulfoxide administered intravenously to horses.

Dimethyl sulfoxide (DMSO) was administered IV to 6 Thoroughbred horses at 2 dosages: 1.0 g/kg and 0.1 g/kg. The pharmacokinetics seemed linear, with biological half-lives of 8.6 +/- 0.3 hours and 9.8 +/- 2.2 hours for the 1.0 g/kg and 0.1 g/kg dosages, respectively. This was further substantiated by mean residence times of 9.8 +/- 0.44 hours and 13.8 +/- 4.25 hours, areas under the curve of 12.55 +/- 1.42 mg/ml/hr and 1.63 +/- 0.49 mg/ml/hr, and the clearances of 0.081 +/- 0.009 L/kg/hr and 0.066 +/- 0.022 L/kg/hr for the large and small dosages, respectively. At 12 hours after 1.0 g/kg was administered, 26.6% of the DMSO dose was excreted unchanged into the urine; at 12 hours after 0.1 g/kg was administered, 25.3% of the DMSO dose was excreted unchanged into the urine. It was predicted that 29.4% and 40.6% of the total DMSO dose would be excreted into the urine for the 1.0 g/kg and 0.1 g/kg dosages, respectively. A 10% DMSO concentration in normal saline solution was safe to give as rapid IV infusion. Slow administration is recommended for more concentrated solutions. Based on the half-life, DMSO should be administered 2 times a day IV for the treatment of increased intracranial pressure and/or cerebral edema in horses.

Animals↗
PubMed1985

Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses.

Phenylbutazone was administered to six Thoroughbred horses in a cross-over study in which the horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half-life of phenylbutazone did not change with cimetidine pretreatment; however, lower plasma concentrations of the metabolite gamma-hydroxyphenylbutazone were observed with cimetidine pretreatments. Plasma concentrations of the metabolite oxyphenbutazone were unchanged with cimetidine pretreatment compared to control values. Twenty-four-hour plasma concentrations of phenylbutazone were not different from control values with cimetidine pretreatment. This study suggests that concurrent treatment with cimetidine and phenylbutazone 24 h before race time does not result in elevations of plasma phenylbutazone concentrations above control values.

Administration, Oral↗
PubMed1984

Large scale extraction of pyrrolizidine alkaloids from tansy ragwort (Senecio jacobaea).

A new technique of large-scale pyrrolizidine alkaloid (PA) extraction was developed in response to toxicity studies on food animals. Results of toxicity experiments on cattle vary from those on rodents (2); therefore, dose/response studies need to be germaine to the appropriate species. This new technique for extraction utilizes protonation of the ring nitrogen and partition of solvent to preferentially extract the alkaloid. The primary equipment used in the system we developed includes a large stainless-steel extraction/separation tank, holding tanks, and a 100-liter vacuum distillation system. From 23 kg of plant material of Senecio jacobaea , our system was able to produce 8-10 g of alkaloid per run, compared to the 3 g which we achieved using other extraction methods (2,4). Additional advantages of our system include a lower labor cost and the ability to recycle the organic solvent.

Methods↗
PubMed1983

Thin-layer agarose isoelectric focusing: an improved technique for determining sheep hemoglobin type.

An improved technique for rapid screening of sheep flocks for hemoglobin (Hb) type is presented. This technique, isoelectric focusing (IEF) on thin-layer agarose gels is simple, rapid, inexpensive and is suitable for screening large numbers of sheep for Hb type. With this technique, up to 100 sheep blood samples can be prepared, tested and interpreted within 2 h after samples are drawn. The new technique was shown to provide better resolution than polyacrylamide gel electrophoresis (PAGE) and was able to resolve samples in which the Hb had become partially degraded. These same samples could not be resolved by PAGE. The use of a special electroendosmosis-free grade of agarose provided resolution essentially equal to polyacrylamide as a matrix for IEF. The advantages are that the casting of the agarose gels is considerably easier, the focusing of samples is more rapid, staining and destaining times are greatly reduced and hazards from potential neurotoxicity of acrylamide are eliminated. Blood from 138 ewes at the Oregon State University Sheep Center was examined by the new agarose IEF technique to determine and demonstrate its usefulness for screening. No difficulty was encountered with interpretation of any of the samples. Frequencies of the HbA and B alleles were similar to those found in earlier studies when polyacrylamide tube gel electrophoresis was used. The observed frequencies were also similar to those expected with the population in Hardy-Weinberg equilibrium.

Animals↗
PubMed1980

Relationships between hemoglobin type and reproduction, lamb, wool and milk production and health-related traits in crossbred ewes.

Relationships among hemoglobin (Hb) types and production traits were examined in 294 crossbred ewes from North Country Cheviot, Dorset, Finnsheep and Romney rams, and Suffolk and Columbia-type ewes. Hb BB ewe lambs were youngest at first estrus, while Hb AA ewe lambs were oldest. Ewe lamb fertility was similar for Hb AB and Hb BB ewes, and both were superior to Hb AA ewes. When Finnsheep crossbreds were excluded, from which Hb BB was absent, Hb BB ewes had higher ewe lamb fertility than did Hb AB ewes. There was a minor advantage of the A over the B allele in ewe lamb prolificacy. Hb BB ewes were highest, Hb AB ewes were intermediate and Hb AA ewes were lowest for average fertility, prolificacy per ewe lambing, lambs born per ewe exposed to mating, total number of lambs weaned and total kilograms of lamb weaned. Grease wool production, staple length, fiber diameter grade, incidence of medullated fibers and incidence of cotted fleeces all were similar across Hb types. Likewise, Hb type did not affect milk production or composition. Ewes with Hb AB had the lowest incidence of footrot; Hb AA and Hb BB ewes were similar. Ewes with Hb AA had the lowest fecal parasite egg counts, while ewes with Hb AB or Hb BB were similar. Ewes with Hb AA also had the lowest incidence of mastitis, Hb BB ewes were intermediate and Hb AB ewes were highest. The combination of overdominance (as for footrot resistance), beneficial effects of the A allele on health-related traits (as for mastitis and parasite resistance) and the beneficial effect of the B allele on reproductive traits, if real, could partly explain the genetic polymorphism commonly reported at the Hb locus in sheep.

Animals↗