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Biomedical subjects

T Wakefield

Publications and source records attributed to T Wakefield.

At least 19 recordsLinked to original sources

Effect of an acute ergotamine challenge on reproductive hormones in follicular phase heifers and progestin-treated cows.

The objective of this research was to determine if ergotamine, an ergopeptine alkaloid isolated from Neotyphodium-infected grasses and associated with toxicoses in livestock, altered plasma concentrations of reproductive hormones in follicular phase heifers and in cows given a progestin implant. In Experiment 1, blood was sampled for 8h from four cycling heifers 2 days after synchronized luteolysis. Heifers were treated with ergotamine tartrate (19microg/kg) i.v. or saline vehicle in a simple cross-over design after 1h of pre-treatment blood sampling. Heifers received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) prolactin concentrations from 1 to 4h post-treatment and increased (P<0.01) 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) concentrations from 2 to 5h post-treatment. A PGFM response to oxytocin was not detected. In Experiment 2, blood was sampled for 8h from six cycling cows 10 days after receiving a s.c. norgestomet implant. Cows were treated i.v. with ergotamine (20microg/kg) or saline in a simple cross-over design after 1h of pre-treatment blood sampling. Cows received gonadorelin (GnRH, 100microg) i.v. 1h after ergotamine or saline. Cows received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) serum prolactin concentrations by 120min after treatment, with prolactin returning to pre-treatment concentrations by 200min after treatment. Saline-treated cows had lower (P<0.01) prolactin by 280min after treatment. Ergotamine-treated cows had higher (P<0.01) PGFM concentrations compared to saline-treated cows 120-240min after treatments, but the groups exhibited similar increases in PGFM after oxytocin. Plasma LH and FSH concentrations increased to peaks 100-120min after GnRH for both groups. However, the LH response to GnRH was greater (P<0.01) for ergotamine-treated cows. In summary, ergotamine lowered prolactin and elevated PGFM concentrations in follicular phase heifers and cows on norgestomet therapy. Ergotamine increased the LH response to exogenous GnRH in cows with norgestomet implants. These data highlight the potential of ergopeptine alkaloids to affect reproduction through altered endocrine function.

Animals↗

Toxoplasma gondii attachment to host cells is regulated by a calmodulin-like domain protein kinase.

The role of calcium-dependent protein kinases in the invasion of Toxoplasma gondii into its animal host cells was analyzed. KT5926, an inhibitor of calcium-dependent protein kinases in other systems, is known to block the motility of Toxoplasma tachyzoites and their attachment to host cells. In vivo, KT5926 blocks the phosphorylation of only three parasite proteins, and in parasite extracts only a single KT5926-sensitive protein kinase activity was detected. This activity was calcium-dependent but did not require calmodulin. In a search for calcium-dependent protein kinases in Toxoplasma, two members of the class of calmodulin-like domain protein kinases (CDPKs) were detected. TgCDPK2 was only expressed at the mRNA level in tachyzoites, but no protein was detected. TgCDPK1 protein was expressed in Toxoplasma tachyzoites and cofractionated precisely with the peak of KT5926-sensitive protein kinase activity. TgCDPK1 kinase activity was calcium-dependent but did not require calmodulin or phospholipids. TgCDPK1 was found to be inhibited effectively by KT5926 at concentrations that block parasite attachment to host cells. In vitro, TgCDPK1 phosphorylated three parasite proteins that migrated identical to the three KT5926-sensitive phosphoproteins detected in vivo. Based on these observations, a central role is suggested for TgCDPK1 in regulating Toxoplasma motility and host cell invasion.

Alkaloids↗

Multiphase-multistep gadolinium-enhanced MR angiography of the abdominal aorta and runoff vessels.

RATIONALE AND OBJECTIVES: To optimize three-dimensional gadolinium magnetic resonance angiography (3D-Gd-MRA) of the aorta and runoff vessels by addressing fundamentally different requirements for temporal and spatial resolution in a single semiautomated examination. METHODS: The technique was designed to obtain pure arterial-phase 3D-Gd-MR angiograms with adequate spatial resolution for each station while avoiding incomplete enhancement due to delayed filling vessels as well as venous overlay. During gadolinium-chelate infusion, a breath-held multiphase 3D-Gd-MRA scan was initiated in the aorta by automatic triggering, followed by automatic table movement. The acquisition was tailored to the vessels of interest by tilting of the 3D volumes. A spatial resolution of 1.7 x 1.2 x 0.8 mm in the calves was achieved by use of elliptical-centric k-space reordering. Signal-to-noise ratio was maximized with a 12-element peripheral vascular coil. Twelve patients with peripheral vascular disease were studied. RESULTS: In cases of aortic occlusive disease (n = 2), dissections (n = 3), or aneurysms (n = 4), substantially delayed fill-in of reconstituted arteries, false lumens, or aneurysmal segments occurred, which was detected only on the later 3D-Gd-MRA phase. High-resolution arterial-phase scans in the calves were obtained, with only one case of substantial venous overlay. Correlation to digital subtraction angiography revealed excellent agreement of pathological findings. CONCLUSIONS: Multiphase-multistep 3D-Gd-MRA reduces the limitations of standard 3D-Gd-MRA techniques with respect to anatomic coverage, spatial resolution, and nonuniform arterial vessel enhancement.

Adult↗

Ergotamine alters plasma concentrations of glucagon, insulin, cortisol, and triiodothyronine in cows.

Bovine plasma was assayed to determine whether ergotamine, an ergopeptide isolated from endophytic tall fescue, affected cortisol, triiodothyronine, insulin, and glucagon concentrations. In Exp. 1, four heifers received an i.v. bolus injection of ergotamine tartrate (19 microg/kg BW) or saline vehicle in a simple crossover design 2 d after induced luteolysis. Oxytocin (100 USP units) was i.v. administered 4 h after ergotamine or saline. Treatment x time affected (P < .01) respiration rates and plasma concentrations of cortisol, triiodothyronine, insulin, and glucagon. Respiration rates were elevated (P < .01) 2 to 7 h after ergotamine, but they were unchanged after saline. Plasma cortisol concentrations were increased (P < .01) 1 to 3 h after ergotamine but not after saline. Plasma triiodothyronine was elevated 2 h after ergotamine, but it was unchanged in response to saline. Insulin decreased (P < .01) and glucagon increased (P < .01) during the 1st h after ergotamine, but not in response to saline. A second increase (P < .01) of glucagon was observed 3 h after ergotamine. In Exp. 2, six cows were treated with an i.v. bolus injection of ergotamine (20 microg/kg BW) or saline in a simple crossover design 10 d after receiving a s.c. ear implant containing norgestomet. Oxytocin (100 USP units) was i.v. administered 4 h after ergotamine or saline. Treatment x time affected (P < .001) respiration rates, cortisol, insulin, and glucagon and tended to influence (P = .12) triiodothyronine concentrations. Respiration rates were elevated (P < .01) 1 to 7 h after ergotamine but were unaltered by saline. Plasma cortisol was elevated (P < .01) 1 to 5 h after ergotamine, but not in response to saline. Plasma triiodothyronine was elevated (P < .01) 1 to 2 h after ergotamine, but not after saline. Insulin was decreased (P < .01) and glucagon increased (P < .01) within 1 h after ergotamine treatment, but they were not altered by saline. A second increase (P < .01) of glucagon occurred by 4 h after ergotamine. In Exp. 1 and 2, glucagon increased (P < .01) 1 h after oxytocin in saline and ergotamine cows. Results indicate that ergotamine can alter plasma concentrations of hormones that mediate nutrient metabolism and thermoregulation in cattle.

Animal Feed↗

An outreach programme for sexually transmitted infection screening in street sex workers using self-administered samples.

Street sex workers represent an at-risk group of individuals who find it difficult to access mainstream health services. This was a cross-sectional study of street sex workers in Melbourne, Australia using a self-administered method to detect chlamydial, gonorrhoea and trichomonas infections. Of the 81 individuals approached, 63 (78%) (95% CI: 67-86%) agreed to participate. Overall, 87% of the participants obtained their results. Of the 63 participants, 53 (84%) had a past history of injecting drug use (95% CI: 73-92%), and 21 (33%) had a history of a sexually transmitted infection (STI) (95% CI: 22.0-46.3%). Neisseria gonorrhoeae was identified in 7 (11%) participants, Trichomonas vaginalis in 7 (11%), Chlamydia trachomatis in 1 (1.6%). None of the 19 (30%) participants who had been screened for an STI in the preceding 3 months were infected. Our results demonstrated that this method of testing for STIs was acceptable to the street sex workers, and demonstrated a disturbingly high proportion with infections.

Adolescent↗

Animal models for the study of lower extremity chronic venous disease: lessons learned and future needs.

The purpose of this review is to define animal models of chronic venous disease and to demonstrate how animal studies can impact our understanding and treatment of this disorder. To this end an extensive literature search was conducted highlighting potential animal models of chronic lower extremity venous disease. Scientific investigations using animals to study particular aspects of this disease are also reviewed. This review was conducted by members of the Committee on Research of the American Venous Forum to help provide direction for future venous research endeavors. Useful models of chronic venous occlusive disease involve controlled ligation of a major lower limb vein and multiple tributaries. Such a model can provide sustained venous hypertension and studies using this model have confirmed that an isodiametric graft can provide early hemodynamic relief. Models of primary, postphlebitic, and isolated chronic deep venous insufficiency are available for study. Valve repair or transplantation can positively impact the insufficiency observed in these models. Investigations into valve substitutes have generally been disappointing or are undergoing early evaluation. In conclusion, animal models for the study of some aspects of chronic venous disease do exist and have already affected our clinical approach to patients. The scientific study of basic pathophysiology, diagnostics, end-organ response, and long-term surgical treatments of this disorder in well-controlled animal experiments have not been conducted.

Animals↗

Reproductive hormonal responses to ergotamine and ergonovine in cows during the luteal phase of the estrous cycle.

We conducted research to evaluate whether ergot alkaloids associated with endophyte-infected tall fescue could alter plasma concentrations of hormones important to reproductive function in cows. Six primiparous, estrous-cycling Holstein cows nursing calves received single i.v. injections of ergotamine tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design. Each cow received one compound per estrous cycle, d 15 or 16 after estrus, and all compounds over three estrous cycles. Blood samples were collected at 20-min intervals for 40 min before and 240 min after treatments to assess plasma concentrations of prolactin, LH, FSH, and the response by PGF2alpha metabolite 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Ambient temperature and respiratory rates were measured hourly. Ambient temperature averaged 26 degrees C during data collection. Treatment x time was a significant source of variation for respiration rate and plasma concentrations of every hormone evaluated except FSH. Ergotamine elevated (P < .01) respiration rates 2 to 4 h after treatment. Ergotamine and ergonovine reduced (P < .001) plasma concentrations of prolactin for 2 to 4 h after treatment compared to concentrations before treatment. Plasma concentrations of LH were lowered (P < .01) by ergonovine during the 3rd h after treatment and by ergotamine during the 4th h after treatment. Most cows exhibited secretory PGFM responses after ergotamine and ergonovine treatments compared with an absence of a PGFM response in all cows after saline (P < or = .01). Results indicated that ergot alkaloids implicated as causative agents for fescue toxicosis can alter plasma concentrations of reproductive hormones during the late luteal phase of the estrous cycle in cows.

Animals↗

Effect of ergotamine and ergonovine on plasma concentrations of thyroid hormones and cortisol in cattle.

Plasma samples from two experiments were processed to determine whether ergot alkaloids associated with endophyte-infected tall fescue altered peripheral thyroxine (T4), triiodothyronine (T3), or cortisol concentrations in cattle. In Exp. 1, seven Angus steers (294 kg) received i.v. bolus injections of saline (SAL), ergonovine maleate (7 mg; EM), or ergotamine tartrate (7 mg; ET) at weekly intervals, and they received all treatments during the study. Blood was sampled every 15 min for 5 h, and treatments were given after h 1. Mean ambient temperature was 34 degrees C. Treatment x time affected plasma concentrations of T3 (P < .05) and of cortisol (P < .001) but not that of T4 (P > .2). Plasma T3 concentrations were not affected by SAL, whereas concentrations increased (P < .01) after either EM or ET treatment. Plasma cortisol concentrations were not altered by SAL or EM, but they were increased (P < .001) by ET treatment. In Exp. 2, six Holstein cows (499 kg) nursing calves received a bolus i.v. injection of SAL, EM (9.5 mg), or ET (9.5 mg) per estrous cycle, and all treatments were given over three cycles. Blood was sampled every 20 min for 5 h; treatments were given after h 1. Mean ambient temperature was 26 degrees C. Treatment x time affected T3 (P = .08) and cortisol (P < .001) and tended to influence (P = .16) T4 concentrations. Plasma T3, T4, and cortisol concentrations were not influenced by SAL treatment. Plasma T3 was higher (P < or = .01) after EM or ET treatment compared with pretreatment concentrations. Concentrations of T4 during the 4 h after EM and ET were increased (P < .001) compared with pretreatment. Plasma cortisol concentrations were not altered by EM but were increased (P < .001) by ET. Ergot alkaloids implicated as contributing agents to fescue toxicosis alter plasma concentrations of hormones important to metabolic and thermoregulatory functions in cattle.

Animals↗

The expression of Toxoplasma proteins in Neospora caninum and the identification of a gene encoding a novel rhoptry protein.

Genes for the Toxoplasma gondii dense granule and rhoptry proteins nucleoside triphosphate hydrolase 3 and ROP2 were expressed at high levels in the closely related parasite N. caninum. The protein products were processed appropriately and were targeted to their correct secretory organelles. NTPase 3 was secreted into the parasitophorous vacuole. The utility of this system was demonstrated in the analysis of a new open reading frame identified upstream of two identical copies of the ROP2 gene. The unknown open reading frame was introduced into Neospora, and transfected parasites were analyzed by immunoblot with antibodies to known T. gondii rhoptry protein families. The transfected Neospora expressed a novel 52 kDa protein, designated ROP8, which localized in the rhoptries. These results illustrate that transfection of known Toxoplasma genes into N. caninum can be used to study their expression, processing and targeting in an immunologically distinct background. They also illustrate the usefulness of N. caninum transfection in the identification and subcellular distribution of proteins encoded by previously uncharacterized Toxoplasma genes.

Acid Anhydride Hydrolases↗

Within- and between-generation effects of temperature on early fecundity of Drosophila melanogaster.

We used a repeated-measures, four-factor experimental design to determine how the fecundity of Drosophila melanogaster during the first 5 days of adult life was influenced by paternal, maternal, developmental and laying temperature, with two different temperature levels (18 degrees C vs. 25 degrees C) per factor. Laying temperature had by far the largest effect on fecundity and accounted for 79 per cent of the variance in overall fecundity: flies laying at 25 degrees C began laying eggs about a day earlier and had much higher daily fecundities than did those laying at 18 degrees C. Developmental temperature had no significant effect either on overall fecundity or on the pattern of daily egg production. Dam temperature had a slight effect on the pattern of daily egg production, but not on overall fecundity. In contrast, sire temperature slightly influenced both overall fecundity and the pattern of daily egg production. Our results demonstrate that early fecundity is extraordinarily sensitive to laying temperature (360 per cent increase if laying at 25 degrees C vs. at 18 degrees C), but is relatively well buffered against developmental and cross-generational effects (maximum effect only 7 per cent, for sire temperature).

Animals↗

Colocutaneous fistula complicating Tenckhoff catheter placement for intraperitoneal chemotherapy.

In view of the characteristic intra-abdominal spread of carcinoma of the colon and rectum [1-3], the use of intraperitoneal chemotherapy may offer an alternative to intravenous or oral drug therapy and even radiation therapy for recurrent disease [4,5]. Several investigators have demonstrated that intraperitoneal drug administration may result in portal vein levels ten to 20 times higher than those observed in peripheral venous blood samples [6]. Traditionally, intraperitoneal chemotherapy has been administered through the Tenckhoff catheter system which was originally developed for peritoneal dialysis in patients with acute or chronic renal failure [7,8]. We report a case of Tenckhoff catheter erosion into the colon with subsequent fistulization developing 20 days after intra-operative placement for intraperitoneal or "belly bath" chemotherapy; this complication occurred in a patient with locally recurrent colorectal adenocarcinoma in whom pelvic peritoneal implants without hepatic metastases were identified at reoperation. This complication of the Tenckhoff catheter system has not previously been reported in the surgical literature.

Antineoplastic Agents↗

The iron status of Black and white female adolescents from eight Southern states.

Hb, hematocrit, plasma iron, and transferrin saturation were measured in approximately 1000 girls aged 12, 14, or 16 yr in eight southern states. The iron status parameters did not differ significantly among the three age groupings or between menstruating and nonmenstruating girls. Blacks had significantly lower mean Hb (p less than 0.0001), hematocrit (p less than 0.0001), and transferrin saturation (p less than 0.05) levels than whites and a greater proportion of Blacks exhibited low Hb (p less than 0.05) and low hematocrit levels (p less than 0.01). Adjusting for dietary iron intakes and per capita income levels did not adequately account for significant race differences for iron status parameters. These findings support the contention that genetic as well as environmental factors are responsible for the frequently reported Black-white differences in Hb and hematocrit levels.

Adolescent↗

Relationships among anthropometric indices of growth and creatinine and hydroxyproline excretion in preadolescent black and white girls.

Relationships among anthropometric indices of growth and creatinine and hydroxyproline excretion were studied over a 2-year longitudinal period in 124 preadolescent girls. Four groups of girls were selected: low-income white (LIW), middle-income white (MIW), low-income black (LIB) and middle-income black (MIB). Changes in body height, weight, subcapsular skinfold, bone density of the phalanx and bone mineral of the radius and ulna were used as indices of growth in relation to creatinine and hydroxyproline excretion. There were no significant differences in subcapsular skinfold among the groups. Bone density of the phalanx and bone mineral of the radius and ulna were significantly greater in blacks than whites at each age. Mean values for urinary creatinine concentration ranged from 0.115 to 0.209 g/dl from 9 to 11 years of age and tended to be greater for the middle-income than the low-income girls. Urinary hydroxyproline (g)/creatinine (g) ranged from 0.072 at 9 to 0.128 at 11 years of age with no significant differences between groups. All measurements showed significant increases with age. Significant positive correlations were seen among several indices in both racial groups and are discussed. INDEX WORDS: Growth, height/weight, hydroxyproline/creatinine excretion, race-income groups, subscapular skinfold, bone density, bone mineral content, preadolescent girls.

Black People↗

Effect of exercise on tissue lipids and serum lipoproteins of rats fed two levels of fat.

Adult rats were fed a low fat (4%) or a high fat (40%) diet, and groups of other rats selected for good running were fed these two diets and were treadmill exercised 5 days a week for 6 weeks. The serum triglycerides were significantly lower in exercised rats fed the low fat diet, but not in those fed the high fat diet, as compared with corresponding controls. The liver lipids were vastly elevated in sedentary rats fed the high fat diet as compared with those fed the low fat diet. An interesting effect of exercise was reflected by the near normal liver lipid levels in rats fed the high fat diet and exercised. However, in these animals, the muscle concentration of cholesterol was significantly higher than that in all other groups. The very low density lipoproteins tended to be lower while the low density lipoproteins tended to be greater in exercised as compared with sedentary rats. It was suggested that the decline in very low density lipoproteins was due to decreased synthesis resulting from adaptive changes in the exercised animal. It was further postulated that the increase in low density lipoproteins was possibly due to increased synthesis necessitated by the need to enhance the catabolism and excretion of cholesterol in exercised animals.

Animal Nutritional Physiological Phenomena↗

The influence of a high level of corn oil on rat serum lipoproteins.

Although the stated requirement for linoleic acid in humans is less than 2% of the dietary calories, recently there has been considerable emphasis on the necessity to substitute dietary polyunsaturates for saturates in order to reduce serum cholesterol levels. In this study we have sought to determine the nutritional consequences of feeding a very high level of linoleate to rats. Three groups of thirty adult animals each were fed a semipurified diet consisting by weight of casein 17%; mineral mixture 5.5%; vitamin mixture in glucose 2.2%; cellulose fiber 3.0%; and corn oil 0% (group A), 10% (group B) or 40% (group C), which was provided at the expense of glucose. At the end of four weeks on the diets, blood was obtained in the fasting state from 16 rats in each group. The serum was ultracentrifugally fractionated into six classes of lipoproteins and analyzed for lipid composition and protein content. Disc gel electrophoresis using lipid and protein stains established that the various lipoprotein subclasses were reasonably free of adjacent density fractions. Although the total serum cholesterol levels were practically the same in the three groups, the cholesterol moiety of the major low density lipoproteins, LDL2 (d 1.019-1.050), but not of very low density lipoproteins, VLDL (d 1.006) or low density lipoproteins, LDL1 (d 1.006-1.019), was substantially and very significantly increased in rats fed the high level of corn oil as compared to the other groups. The concentration of the very low density lipoproteins was significantly lower in group C than in the groups A and B. The LDL2 concentration but not that of LDL1 was significantly greater in group C as compared to group A. The cholesterol/total lipid ratio was significantly greater in both LDL2 and LDL1 but not in VLDL of group C as compared with group A. The serum high density lipoproteins were relatively less influenced by the ingestion of an excessive level of corn oil at this time period. The serum lipoprotein levels as well as their lipid composition were generally similar in groups A and B and suggested that a moderate level (5%) of dietary linoleate did not cause any untoward changes in rats. On the basis of current information on the metabolism of lipoproteins, it has been proposed that the increase in rat serum LDL2 of group C reflects the status of the liver and that a large portion of the cholesterol moiety of LDL2 is perhaps derived from the liver while the protein and phospholipid portions may represent remnants of VLDL catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗