Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases.

Cervical clear cell carcinoma (CCC) is a rare human papillomavirus-independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus-associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6%), and the majority were treated with radical surgery (84.5%) and adjuvant therapy (55.2%). Lymphovascular invasion was present in 31%, while lymph node metastasis was seen in 24.1%; 10.3% were associated with abdominopelvic metastases at the time of diagnosis; 32.8% had recurrences, and 19% died of disease. We did not find statistically significant differences in OS and RFS between CCC and GTA at 5 and 10 years (P=0.313 and 0.508, respectively), but there were significant differences in both OS and RFS between CCC and HPVA ECA (P=0.003 and 0.032, respectively). Also, OS and RFS in stage I clear cell and GTA were similar (P=0.632 and 0.692, respectively). Multivariate analysis showed that OS is influenced by the presence of recurrence (P=0.009), while RFS is influenced by the FIGO stage (P=0.025). Cervical CCC has poorer outcomes than HPVA ECA and similar outcomes to human papillomavirus-independent GTA. Oncologic treatment significantly influences RFS in univariate analysis but is not an independent prognostic factor in multivariate analysis suggesting that alternative therapies should be investigated.

The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis.

BACKGROUND: Caffeine is a widely used ergogenic aid with most research suggesting it confers the greatest effects during endurance activities. Despite the growing body of literature around the use of caffeine as an ergogenic aid, there are few recent meta-analyses that quantitatively assess the effect of caffeine on endurance exercise. OBJECTIVES: To summarise studies that have investigated the ergogenic effects of caffeine on endurance time-trial performance and to quantitatively analyse the results of these studies to gain a better understanding of the magnitude of the ergogenic effect of caffeine on endurance time-trial performance. METHODS: A systematic review was carried out on randomised placebo-controlled studies investigating the effects of caffeine on endurance performance and a meta-analysis was conducted to determine the ergogenic effect of caffeine on endurance time-trial performance. RESULTS: Forty-six studies met the inclusion criteria and were included in the meta-analysis. Caffeine has a small but evident effect on endurance performance when taken in moderate doses (3-6 mg/kg) as well as an overall improvement following caffeine compared to placebo in mean power output (3.03 ± 3.07%; effect size = 0.23 ± 0.15) and time-trial completion time (2.22 ± 2.59%; effect size = 0.41 ± 0.2). However, differences in responses to caffeine ingestion have been shown, with two studies reporting slower time-trial performance, while five studies reported lower mean power output during the time-trial. CONCLUSION: Caffeine can be used effectively as an ergogenic aid when taken in moderate doses, such as during sports when a small increase in endurance performance can lead to significant differences in placements as athletes are often separated by small margins.

Moderate dietary supplementation with vitamin E enhances lymphocyte functionality in the adult cat.

This study aimed to determine the effects of supplemental Vit E and/or Se on selected parameters of the immune system of the cat. Nine diets were fed in a 3 × 3 factorial design with no supplementation (control (C)); and either moderate (M); or high (H) levels of Vit E (0, 225 or 450 mg/kg DM diet) and/or Se (0, 2 or 10 mg/kg DM diet) added to a complete and balanced basal diet. After 28 days of feeding, enhanced lymphocyte proliferative responses to Concanavalin A and phytohaemagglutinin were observed (P < 0.05) in cats fed diets containing supplemental Vit E, irrespective of whether they also contained Se. Cats in the MVitE, HVitE, MVitE + MSe, HVitE + MSe, and HVitE + HSe groups all showed enhancement of phagocytic activity compared to control animals (P < 0.001). Our results indicate that a supplemental level of 225 mg/kg DM diet Vit E appears to have beneficial effects on immune function in the cat.

Carbohydrate supplements and their effects on pasture dry matter intake, feeding behavior, and blood factors associated with intake regulation.

Supplementary feeds are offered to grazing dairy cows to increase dry matter (DM) and metabolizable energy (ME) intakes; however, offering feed supplements reduces pasture DM intake, a phenomenon known as substitution. The objective of the study was to investigate changes in blood factors associated with intake regulation in monogastric species in pasture-fed dairy cows supplemented with either a starch- or nonforage fiber-based concentrate. Fifteen multiparous Friesian × Jersey cross cows were assigned to 1 of 3 treatments at calving. Measurements were undertaken in wk 8 of lactation. Treatments were pasture only, pasture plus a starch-based concentrate (3.5 kg of DM/cow per day; STA), and pasture plus a nonforage fiber-based concentrate (4.4 kg of DM/cow per day). Pelleted concentrates were fed at an isoenergetic rate in 2 equal portions at a.m. and p.m. milkings. Measurements were undertaken to investigate differences in pasture DM intake, feeding behavior, and profiles of blood factors for 4h after a.m. and p.m. milkings, the periods of intensive feeding in grazing cows. Supplementing cows with STA concentrate reduced pasture DM intake to a greater extent than the fiber concentrate, although time spent eating did not differ between treatments. The blood factor response to feeding differed between the a.m. and p.m. feeding events. Blood factors associated with a preprandial or fasted state were elevated prefeeding in the a.m. and declined following feeding, whereas satiety factors increased. In comparison, the blood factor response to feeding in the p.m. differed, with responses to feeding delayed for most factors. Plasma ghrelin concentration increased during the p.m. feeding event, despite the consumption of feed and the positive energy state remaining from the previous a.m. feeding, indicating that environmental factors (e.g., sunset) supersede physiological cues in regulating feeding behavior. The greater reduction in pasture DM intake for the STA treatment in the p.m. may be related to the level of hunger or satiety before the feeding event and not solely to the consumption of supplement. Data indicate that neuroendocrine factors are, at least in part, responsible for the substitution of pasture for supplementary feeds.

Technical note: Nitrogen isotopic fractionation can be used to predict nitrogen-use efficiency in dairy cows fed temperate pasture.

The objective of this study was to investigate the relationship between nitrogen isotopic fractionation (δ(15)N) and nitrogen-use efficiency (milk nitrogen/nitrogen intake; NUE) in pasture-fed dairy cows supplemented with increasing levels of urea to mimic high rumen degradable protein pastures in spring. Fifteen cows were randomly assigned to freshly cut pasture and either supplemented with 0, 250, or 336 g urea/d. Feed, milk, and plasma were analyzed for δ(15)N, milk and plasma for urea nitrogen concentration, and plasma for ammonia concentration. Treatment effects were tested using ANOVA and relationships between variables were established by linear regression. Lower dry matter intake (P = 0.002) and milk yield (P = 0.002) occurred with the highest urea supplementation (336 g urea/d) compared with the other two treatments. There was a strong linear relationship between milk δ(15)N - feed δ(15)N and NUE: [NUE (%) = 58.9 - 10.17 × milk δ(15)N - feed δ(15)N (‰) (r(2) = 0.83, P < 0.001, SE = 1.67)] and between plasma δ(15)N - feed δ(15)N and NUE: [NUE (%) = 52.4 - 8.61 × plasma δ(15)N - feed δ(15)N (‰) (r(2) = 0.85, P < 0.001, SE = 1.56)] . This study confirmed the potential use of δ(15)N to predict NUE in cows consuming different levels of rumen degradable protein.

Short communication: immediate and deferred milk production responses to concentrate supplements in cows grazing fresh pasture.

The objective of this study was to determine the increase in milk production from supplementation that occurred after supplementation ceased. This portion of the total response (i.e., the deferred response), although accepted, is generally not accounted for in short-term component research projects, but it is important in determining the economic impact of supplementary feeding. Fifty-nine multiparous Holstein-Friesian dairy cows were offered a generous allowance of spring pasture [>45 kg of dry matter (DM)/cow per day) and were supplemented with 0, 3, or 6 kg (DM)/d of pelleted concentrate (half of the allowance at each milking event) in a complete randomized design. Treatments were imposed for the first 12 wk of lactation. Treatments were balanced for cow age (5.4 ± 1.68 yr), calving date (July 27 ± 26.0 d), and genetic merit for milk component yield. During the period of supplementation, milk yield and the yield of milk components increased (1.19 kg of milk, 0.032 kg of fat, 0.048 kg of protein, and 0.058 kg of lactose/kg of concentrate DM consumed), but neither body condition score nor body weight was affected. After concentrate supplementation ceased and cows returned to a common diet of fresh pasture, milk and milk component yields remained greater for 3 wk in the cows previously supplemented. During this 3-wk period, cows that previously received 3 and 6 kg of concentrate DM per day produced an additional 2.3 and 4.5 kg of milk/d, 0.10 and 0.14 kg of fat/d, 0.10 and 0.14 kg of protein/d, and 0.10 and 0.19 kg of lactose/d, respectively, relative to unsupplemented cows. This is equivalent to an additional 0.19 kg of milk, 0.006 kg of fat, 0.006 kg of protein, and 0.008 kg of lactose per 1 kg of concentrate DM previously consumed, which would not be accounted for in the immediate response. As a result of this deferred response to supplements, the total milk production benefit to concentrate supplements is between 7% (lactose yield) and 32% (fat yield) greater than the marginal response measured during the component experiment. Recommendations to dairy producers based on component feeding studies must be revised to include this deferred response.

Dietary structural to nonfiber carbohydrate concentration during the transition period in grazing dairy cows.

A study was conducted to evaluate the potential effects of altering the proportion of dietary structural carbohydrate (SC) relative to nonfiber carbohydrate (NFC) pre- and postpartum on milk production and the circulating concentrations of hormones and metabolites. Dietary treatments were arranged as a 2 x 2 factorial, with 68 multiparous cows assigned to isoenergetic diets [114 MJ of metabolizable energy (ME)/cow per d] precalving; diets were either fresh pasture and pasture silage (PreP) or pasture and pasture silage supplemented with 3 kg dry matter (DM)/cow per d of a corn- and barley-based concentrate for 36 d prepartum (PreC). Final treatments were 13 or 32% DM NFC, respectively. After calving, cows within each prepartum diet were assigned to isoenergetic diets (179 MJ of ME/cow per d) differing in their SC and NFC content. Postcalving diets were either fresh pasture and pasture silage (PostP) or pasture and pasture silage supplemented with 5 kg DM/cow per d of a corn- and barley-based concentrate (PostC) until 35 d in milk. Final treatments were 18 and 38% DM NFC, respectively. Relative to day of calving (d 0), blood samples were collected at least weekly from d -28 to d 35. During the prepartum period, PreC cows had lower plasma urea, albumin, insulin-like growth factor-I, and Ca concentrations, but greater nonesterified fatty acid and Mg concentrations. There were no evident effects of prepartum diet on body weight or body condition score, milk yield, or milk composition. During the postpartum period, PostC cows had lower concentrations of plasma urea, beta-hydroxybutyrate, and Ca, but greater concentrations of nonesterified fatty acids, glucose, insulin-like growth factor-I, and Mg. Postpartum metabolic differences in PostC cows were associated with increased milk protein production and reduced milk fat (yield and %). Results do not support a periparturient metabolic benefit to altering the SC to NFC ratio precalving, but imply an altered rumen fermentation, gluconeogenesis, and milk composition when dietary SC to NFC ratio is altered postcalving.

Extending lactation in pasture-based dairy cows. II: Effect of genetic strain and diet on plasma hormone and metabolite concentrations.

Fifty-six genetically divergent New Zealand and North American Holstein-Friesian (HF) cows grazed pasture, and were offered 0, 3, or 6 kg of concentrate DM/cow per day for an extended lactation (605 +/- 8.3 d in milk; mean +/- standard error of the mean). Weekly blood samples collected from individual cows from wk 1 to 10 postpartum (early lactation), and from wk 47 to 63 postpartum (extended lactation) were analyzed for nonesterified fatty acids (NEFA), glucose, insulin, leptin, growth hormone (GH), insulin-like growth factor-I (IGF-I), calcium, and urea. During early lactation, NEFA and GH concentrations were greater and IGF-I concentrations were less, and increased at a slower rate in North American HF. During this 10-wk period, there were no strain effects on plasma glucose, leptin, insulin, or calcium. During the extended lactation period, North American HF had greater NEFA and GH concentrations; there were strain x diet interactions for insulin and leptin, and a tendency for a strain x diet interaction for glucose. These interactions were primarily due to greater plasma insulin, leptin, and glucose concentrations in the New Zealand HF fed 6 kg of concentrate DM/cow per day, a result of excessive body condition in this treatment. In this period, there was no strain effect on plasma IGF-I, calcium, or urea concentration. During early lactation, there was a linear increase in glucose and IGF-I, and a linear decrease in GH and urea with increasing concentrate in the diet. However, plasma calcium, NEFA, insulin, and leptin remained unchanged. During the extended lactation period, there was an effect of feed supplementation on GH and urea, which decreased linearly with increasing concentrate in the diet. There was, however, no supplementation effect on NEFA, calcium, or IGF-I. These data indicate potential strain differences in recoupling of the somatotropic axis, insulin resistance, and energy partitioning, and may help explain the physiology behind the previously reported greater milk production and body condition score loss in North American HF. The results have implications for breeding and diet management during an extended lactation.

Pediatric radical abdominal trachelectomy for anaplastic embryonal rhabdomyosarcoma of the uterine cervix: an alternative to radical hysterectomy.

Rhabdomyosarcoma arising in the female genital tract carries 5-year survival in excess of 80%, but lifelong infertility may be a consequence of local control strategies. We present the technique and outcome for a fertility-sparing, radical abdominal trachelectomy in a 12-year-old girl with anaplastic, embryonal rhabdomyosarcoma involving the uterine cervix. The patient had presented to our center after the piecemeal resection of a uterine cervical mass; because of concern about microscopic residual disease, we classified her as group II-A according to the Intergroup Rhabdomyosarcoma Study system. Staging studies excluded the presence of distant disease. The patient received 4 cycles of multiagent chemotherapy and then underwent radical abdominal trachelectomy, with removal of the uterine cervix, parametria, vaginal cuff, and regional lymph nodes. Microscopically, the specimen showed treatment effect and no residual tumor. Regional nodes were negative. Radical abdominal trachelectomy, which has not been previously reported for rhabdomyosarcoma, has appeared to secure local disease control in this case while preserving the patient's future fertility potential. In properly selected cases of rhabdomyosarcoma of the uterine cervix, where involvement of the uterus proper is not present, radical abdominal trachelectomy may be an attractive fertility-sparing alternative to radical hysterectomy.

Urinary felinine excretion in intact male cats is increased by dietary cystine.

Felinine is a branched-chain sulfur amino acid present in the urine of certain Felidae, including domestic cats. The objective of the present study was to determine if additional cystine and/or dietary N would increase felinine and N-acetylfelinine excretion by intact male cats fed a low-protein(LP) diet. Feeding five adult intact male cats an LP diet (18.8% of metabolisable energy (ME) as protein) v. a high-protein diet (38.6% of ME as protein) resulted in a trend (P=0.08) for decreased urinary felinine and no change in N-acetylfelinine excretion. In a 23 d study, when the LP diet was supplemented with L-cystine at 9.3 g/kg DM, urinary felinine:creatinine ratio showed a linear two-fold (121 %) increase (P<0.01) from 0.24 (SEM 0.05) to 0.53 (SEM 0.13) after 10 d. Subsequent feeding of the LP diet resulted in a decrease in felinine excretion to base levels. Plasma gamma-glutamyl felinylglycine concentrations were consistent with the excretion of felinine. Supplementation of the LP diet with L-cystine (9.3 g/kg DM),dispensable amino acids and arginine to a second group (n 5) also resulted in a significant (P<0.01) but smaller (+72 %) increase in the daily felinine:creatinine ratio (0.25 (SEM 0.04) to 0.43 (SEM 0.05)). The degree of felinine N-acetylation within groups was unaffected by dietary addition and withdrawal of amino acids. The results indicate that felinine synthesis is regulated by cystine availability, and that arginine may be physiologically important in decreasing felinine biosynthesis in intact male cats.

Effects of a supplement containing trans-10, cis-12 conjugated linoleic acid on bioenergetic and milk production parameters in grazing dairy cows offered ad libitum or restricted pasture.

Conjugated linoleic acid (CLA) reduces milk fat synthesis in grazing dairy cows and may improve calculated net energy balance (EBAL). Study objectives were to determine whether CLA-induced milk fat depression could be utilized during times of feed restriction to improve bioenergetic and milk production parameters. Twelve multiparous rumen-fistulated Holstein cows (204 +/- 7 d in milk) were offered ad libitum (AL) or restricted (R) pasture and abomasally infused twice daily with 0 (control) or 50 g/d of CLA (CLA; mixed isomers) in a 2-period crossover design. Treatment periods lasted 10 d and were separated by a 10-d washout period. Milk and plasma samples were averaged from d 9 and 10, and EBAL was calculated from d 6 to 10 of the infusion period. Pasture restriction reduced the yield of milk (3.9 kg/d) and milk components. The CLA treatment reduced milk fat yield by 44 and 46% in AL and R, respectively. There was no effect of CLA on milk yield or milk lactose content or yield in either feeding regimen; however, CLA increased the milk protein content and yield by 7 and 6% and by 5 and 8%, in AL and R, respectively. The CLA-induced changes to milk fat and protein doubled the protein:fat ratio in both AL and R. Calculated EBAL improved following the CLA infusion (-0.44 vs. 2.68 and 0.38 vs. 3.29 Mcal/d for AL and R, respectively); however, CLA did not alter plasma bioenergetic markers. Data indicate that during short periods of nutrient limitation, supplemental CLA may be an alternative management tool to enhance protein synthesis and improve the milk protein:fat ratio and calculated EBAL in cows grazing pasture. Further studies are required to determine whether CLA is effective at improving bioenergetic and production parameters during more severe or longer term nutrient restriction.

The effect of bovine colostrum supplementation on salivary IgA in distance runners.

Secretory IgA in saliva (s-IgA) is a potential mucosal immune correlate of upper respiratory tract infection (URTI) status. Nutritional supplements may improve mucosal immunity, and could be beneficial to athletes who are at increased risk of URTI. In this study, 35 distance runners (15 female, 20 male, age 35 to 58 y) consumed a supplement of either bovine colostrum or placebo for 12 wk. Saliva samples were taken prior to training at baseline, monthly during supplementation, and 2 wk post supplementation. Median levels of s-IgA increased by 79% in the colostrum group after 12 wk intervention, and the time-dependent change from baseline value was significant (P = 0.0291). This significance was still apparent after adjusting for training volume and self-reporting of upper respiratory symptoms. This study has demonstrated increased s-IgA levels among a cohort of athletes following colostrum supplementation. While this result is statistically significant, its physiological interpretation must be viewed with caution due to the small numbers in this study and the large variability in s-IgA levels.

Patient safety: mindful, meaningful, and fulfilling.

Five years after the landmark report of the Institute of Medicine To Err Is Human (Kohn, Corrigan, and Donaldson 2000), many are asking, "Is U.S. healthcare safer?" A number of articles addressing this question have been written, interviews with nationally recognized patient safety leaders have been published, and governing boards of many healthcare organizations are examining reports of care provided by their institutions. Robert M. Wachter, writing in the November 2004 issue of Health Affairs, concludes that, "At this point, I would give our efforts an overall grade of C+, with striking areas of progress tempered by clear opportunities for improvement." We describe in this article the pursuit of a culture of safety at William Beaumont Hospital in Royal Oak, Michigan. Our experience has offered us the opportunity to ponder a number of key questions: How does leadership guide an organization toward a culture of safety? Does culture truly drive behavior, or is it really the reverse? How can a culture of safety be measured or observed? What levels of resources and commitment are required for success? Is safety all about systems and processes, or are core values also involved? What role does the patient play in ensuring safe care? We attempt to offer guidance, and share lessons learned, for each of these important questions.

Effect of supplemental conjugated linoleic acids on heat-stressed brown swiss and holstein cows.

Heat-stressed dairy cattle are bioenergetically similar to early-lactation cows in that dietary energy may be inadequate to support maximum milk and milk component synthesis. Study objectives were to evaluate whether conjugated linoleic acids- (CLA-) induced milk fat depression (MFD) during heat stress would allow for increased milk and milk component synthesis. In addition, CLA effects on production variables and its ability to induce MFD were compared between Holstein and Brown Swiss cows. Multiparous cows (n = 8, Holstein; n = 5, Brown Swiss) averaging 97 +/- 17 d in milk were used in a crossover design during the summer (mean temperature-humidity index = 75.7). Treatment periods were 21 d with a 7-d adaptation period before and between periods. During adaptation periods, all cows received a supplement of palm fatty acid distillate (242 g/d). Dietary treatment consisted of 250 g/d of CLA supplement (78.9 g/d of CLA) or 242 g/d of palm fatty acid distillate to provide equal amounts of fatty acids. The CLA supplement contained a variety of CLA isomers (3.0% trans-8, cis-10; 3.4% cis-9, trans-11; 4.5% trans-10, cis-12; and 4.8% cis-11, trans-13 CLA). Treatments were applied 2 x/d with half of the supplement top-dressed at 0600 h and the remainder top-dressed at 1800 h. There was no overall treatment effect on dry matter intake (23.9 kg/d), milk yield (40.0 kg/d), somatic cell count (305,000), protein (2.86%), or lactose content (4.51%) or yields of these milk components. Supplementation with CLA decreased overall milk fat content and yield by 26 and 30%, irrespective of breed. The reduction of milk fat content and yield was greatest on d 21 (28 and 37%, respectively). Energy availability predicted by energy balance was improved with CLA supplementation compared with controls (3.7 vs. 7.1 Mcal/d, respectively). Respiration rate (78 breaths/min) and skin temperature (35.4 degrees C) during maximum heat load were not affected by treatment. The group receiving CLA had higher total milk fat CLA concentration (9.3 vs. 4.9 mg/g). Supplementation with CLA induced MFD and altered milk fat composition similarly between breeds and improved calculated energy balance during heat stress, but had no effect on production measures under these conditions.

Endogenous synthesis of cis-9, trans-11 conjugated linoleic acid in dairy cows fed fresh pasture.

New Zealand Holstein-Friesian cows (n = 4) were used to quantify the importance of endogenous synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) via Delta(9)-desaturase in cows fed a fresh pasture diet. The experiment was a 4 x 4 Latin square design with treatments arranged in a 2 x 2 factorial. Treatments lasted 4 d and were pasture only, pasture plus sterculic oil, pasture plus sunflower oil, and pasture plus sunflower oil plus sterculic oil. Abomasal infusion of sterculic oil inhibited Delta(9)-desaturase and decreased the concentration of cis-9, trans-11 CLA in milk fat by 70%. Using the changes in cis-9 10:1, cis-9 12:1 and cis-9 14:1 to correct for incomplete inhibition of Delta(9)-desaturase, a minimum estimate of 91% of cis-9, trans-11 CLA in milk fat was produced endogenously in cows fed fresh pasture. Dietary supplementation of a pasture diet with sunflower oil increased the proportion of long chain fatty acids in milk fat; however, the increase in vaccenic acid concentration was small (18%) and there was no increase in cis-9, trans-11 CLA concentration. Overall, results show that endogenous synthesis is responsible for more than 91% of the cis-9, trans-11 CLA secreted in milk fat of cows fed fresh pasture. However, the failure of plant oil supplements to increase the concentration of cis-9, trans-11 CLA in milk fat from pasture-fed cows requires further investigation.

Effects of abomasal infusion of conjugated linoleic acid on milk fat concentration and yield from pasture-fed dairy cows.

The aim of this study was to investigate the effects of conjugated linoleic acid supplementation on the synthesis of milk fat in pasture-fed Friesian cows. In four cows, a commercial mixture containing 62.3% (wt/vol) conjugated linoleic acid was infused intraabomasally to avoid rumen fermentation and biohydrogenation. The design was a 4 x 4 Latin square in which each cow received infusions of 0, 20, 40, and 80 g/d of conjugated linoleic acid mixture for 4 d. Cows were fed freshly cut ryegrass/white clover pasture ad libitum. Milk fat concentration was decreased by 36, 43, and 62% and milk fat yield was decreased by 32, 36, and 60% by the 20, 40, and 80 g of conjugated linoleic acid/d treatments. Dry matter intake, milk protein concentration, and protein yield were unaffected by treatments; however, milk yield was increased by 11% during the 40-g conjugated linoleic acid/d treatment. The effects of conjugated linoleic acid infusion were most pronounced in reducing de novo fatty acid synthesis and desaturation. Results show that the inhibitory effect of this conjugated linoleic acid mixture on milk fat synthesis occurs in pasture-fed cows, and demonstrate the potential to dramatically alter gross milk composition. This technology could offer a management tool to manipulate milk composition and energy demands of pasture-fed cows.

Regulation of human and mouse procathepsin E gene expression.

Cathepsin E is an intracellular aspartic proteinase that is considered to have a number of physiological roles including antigen processing. Quantitation of procathepsin E mRNA by LightCyclertrade mark technology indicated that the gene was transcribed in lung but not in kidney of both human and mouse origin. In contrast, the transcript was present in mouse spleen and alveolar macrophages but not in the counterpart tissue/cells from humans. Regulation of human and mouse procathepsin E gene expression was shown not to be influenced by the extent of CpG methylation but depended on the recognition of potential binding motifs in each promoter region by transcription factors such as GATA1, PU1 and YY1, as revealed by functional analysis using a series of promoter/luciferase reporter gene fusion constructs. Thus the extent to which the procathepsin E gene is expressed in a particular cell type may depend on the balance between the effects produced by positive-acting, cell-specific transcription factors such as GATA1 and PU1 and the negative influence of the ubiquitous YY1 factor. In this way, the relative abundance and influence of general and cell-specific transcription factors can govern the production of cathepsin E and thereby account for the sporadic cell and tissue distribution of this enzyme in different species.

Effect of posture and isoproterenol on beat-to-beat heart rate and QT variability.

RATIONALE: Recent literature emphasizes the utility of QT variability to study ventricular electrophysiologic function. In this investigation, we sought to test the hypothesis that beat-to-beat fluctuations in QT intervals are mediated by sympathetic activity in normal subjects using postural challenge and isoproterenol infusions. SUBJECTS AND METHODS: We obtained ECG in the supine and standing postures during spontaneous breathing, at 12, 15 and 20 per minute controlled breathing (n = 19), and before and after infusions of isoproterenol, a beta-adrenergic agent, in the supine posture during spontaneous breathing (n = 11) using lead II configuration in healthy human adult subjects. Heart rate (HR) and QT time series data were analyzed by spectral analysis of 256 s of real-time data. Beat-to-beat QT intervals were measured by automated analysis of ECG. A QT variability index (QT(vi)) was calculated for each subject as the logarithm of the ratio of normalized QT variance to normalized HR variance. We also calculated fractal dimensions of QT time series during spontaneous breathing. RESULTS: QT(vi) was significantly higher in the standing than in the supine posture (-1. 93 +/- 0.27 vs. -1.47 +/- 0.41; p = 0.0001), and also during isoproterenol infusions in the supine posture (-1.83 +/- 0.39 vs. -1. 27 +/- 0.43; p = 0.0001). Fractal dimensions of QT time series were also significantly higher during standing (p = 0.00001) and isoproterenol infusions (p = 0.0002). Respiratory rate or tidal volume did not account for the increased QT variability seen in the standing posture. CONCLUSIONS: A change from the supine to the standing posture as well as infusion of isoproterenol significantly increased the absolute as well as normalized QT variability, which appears to be due to an increase in sympathetic activity associated with these conditions.