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J L Ellis

Publications and source records attributed to J L Ellis.

At least 19 recordsLinked to original sources

Evaluation of net energy expenditures of dairy cows according to body weight changes over a full lactation.

Equations that predict daily dry matter intake (DMI) of a lactating cow could be evaluated by comparing the predicted accumulation of energy in body weight (BW) over the course of lactation with the observed BW evolution. However, to do so requires that first the energy balance calculations from observed DMI are evaluated. The purpose of the work reported here was to determine the degree of deviation of predicted from observed BW, according to net energy for lactation (NE(L)) balance calculated from weekly observations of DMI, BW, and fat-corrected milk production in 21 sets of full-lactation data, and to determine an appropriate correction of the NE(L) bias for subsequent DMI prediction evaluations. When the National Research Council maintenance equation 0.08 x BW(kg)(0.75) was used in energy balance calculation, BW was overpredicted with an increasing difference between the cumulative predicted BW and observed BW as lactation progressed. Placing all the error of BW prediction into maintenance energy expenditures resulted in a best-fit equation of 0.096 +/- 0.003 Mcal/kg of BW(0.75). A time-dependent equation was also developed, in which weekly maintenance expenditures were determined as the NE(L) expenditure to yield a zero NE(L) balance and could be described by a second-order polynomial equation related to week of lactation (WOL) where maintenance NE(L) = [-0.0227(+/- 0.0098) x WOL2 + 1.352(+/- 0.456) x WOL + 78.09(+/- 4.92) Mcal/kg of BW(0.75)] x 10(-3). Average maintenance energy expenditure at the onset of lactation was approximately 0.08 Mcal/kg of BW(0.75), and this value increased to a plateau at wk 15 of lactation of approximately 0.098 Mcal/kg of BW(0.75). Standard deviations between data sets of weekly maintenance parameter estimates throughout lactation were large but consistent at approximately 25% of the mean. Revision of the maintenance energy expenditure estimate substantially improved BW prediction by the energy balance model. On average, the 0.096 Mcal of NE(L)/kg of BW(0.75) equation resulted in the best BW predictions, although substantial variation existed around this value.

Animals↗

Prediction of dry matter intake throughout lactation in a dynamic model of dairy cow performance.

In the dynamic modeling of dairy cow performance over a full lactation, the difference between net energy intake and net energy used for maintenance, growth, and output in milk accumulates in body reserves. A simple dynamic model of net energy balance was constructed to select, out of some common dry matter intake (DMI) prediction equations, the one that resulted in a minimum cumulative bias in body energy deposition. Dry matter intake was predicted using the Cornell Net Carbohydrate and Protein System, Agricultural Research Council, or National Research Council (NRC) DMI equations from body weight (BW) and predicted fat-corrected milk yield. The instantaneous BW of cows at progressive weeks of lactation was simulated as the numerical integral of the BW change obtained from the predicted net energy balance. Predicted DMI and BW from each DMI equation, using either of 2 equations to describe maintenance energy expenditures, were compared statistically against observed data from 21 herd average published full lactation data sets. All DMI equations underpredicted BW and DMI, but the NRC DMI equation resulted in the minimum cumulative error in predicted BW and DMI. As a general solution to prevent predicted BW from deviating substantially over time from the observed BW, a lipostatic feedback mechanism was integrated into the NRC DMI equation as a 2-parameter linear function of the relative size of simulated body reserves and week of lactation. Residual sum of squares was reduced on average by 52% for BW predictions and by 41% for DMI predictions by inclusion of the negative feedback with parameters taken from the average of all 21 least squares fits. Similarly, root mean square prediction error (%) was reduced by 30% on average for BW predictions and by 23% for DMI predictions. Inclusion of a feedback of energy reserves onto predicted DMI, simulating lipostatic regulation of BW, solved the problem of final BW deviation within a dynamic model and improved its DMI prediction to a satisfactory level.

Adipose Tissue↗

Initial validation of an instrument to identify barriers to self-management for persons with co-morbidities.

OBJECTIVE: To develop and initially validate a questionnaire designed to assess barriers to self-management perceived by persons with multiple chronic medical conditions. We hypothesized that persons who reported increased barriers to self-management would also report lower general health status and a greater disease burden. METHODS: A cross-sectional survey was done of Health Maintenance Organization members aged 65 years or older with varying numbers of chronic medical conditions. On the basis of a previous qualitative investigation, we have identified 13 domains representing potential barriers to self-management. We developed questions to assess each of these domains and, for each, calculated coefficients alpha and assessed correlation of that domain with self-reported general health status and disease burden. RESULTS: Respondents reported an average of 5.9 chronic conditions. Eight domains demonstrated acceptable internal consistency in this population. Nine of 13 domains correlated significantly in the expected direction with health status and/or disease burden. DISCUSSION: These results provide an encouraging first step in developing a tool that will be clinically useful in assessing and addressing barriers to medical self-management for persons with co-morbidities. Use of assessments such as this in clinical settings may facilitate appropriate and efficient care management and improved health outcomes for this growing and vulnerable patient population.

Aged↗

Development of muscarinic analgesics derived from epibatidine: role of the M4 receptor subtype.

Epibatidine, a neurotoxin isolated from the skin of Epipedobates tricolor, is an efficacious antinociceptive agent with a potency 200 times that of morphine. The toxicity of epibatidine, because of its nonspecificity for both peripheral and central nicotinic receptors, precludes its development as an analgesic. During the synthesis of epibatidine analogs we developed potent antinociceptive agents, typified by CMI-936 and CMI-1145, whose antinociception, unlike that of epibatidine, is mediated via muscarinic receptors. Subsequently, we used specific muscarinic toxins and antagonists to delineate the muscarinic receptor subtype involved in the antinociception evoked by these agents. Thus, the antinociception produced by CMI-936 and CMI-1145 is inhibited substantially by 1) intrathecal injection of the specific muscarinic M4 toxin, muscarinic toxin-3; 2) intrathecally administered pertussis toxin, which inhibits the G proteins coupled to M2 and M4 receptors; and 3) s.c. injection of the M2/M4 muscarinic antagonist himbacine. These results demonstrate that the antinociception elicited by these epibatidine analogs is mediated via muscarinic M4 receptors located in the spinal cord. Compounds that specifically target the M4 receptor therefore may be of substantial value as alternative analgesics to the opiates.

Alkaloids↗

Expected neurologic outcomes for surgical treatment of cervical neurilemomas.

OBJECTIVE: Neurilemomas are classically described as fusiform tumors that eccentrically displace the undisturbed neural fascicles. The authors seek to clarify the relationship of cervical neurilemomas to their nerve of origin and assess the functional outcome of surgical extirpation. STUDY DESIGN: A retrospective review of clinical, intraoperative, and histopathologic data of six patients with cervical extracranial neurilemomas. METHODS: Additional histochemical staining of the pathologic specimens was performed to evaluate the tumor for neurites. A comprehensive literature review of cervical neurilemoma cases and meta-analysis of clinical outcomes in these cases were performed. RESULTS: In the series of five consecutive cervical neurilemomas, only one was an eccentric mass pushing the undisturbed nerve aside. In the five other cases, excision of the neurilemoma required complete nerve excision. Neural elements traveling through the central portions of the tumor were clearly demonstrated histologically. Collective analysis of the literature on cervical neurilemomas revealed that although some cases allow nerve preservation, preservation of function is frequently poor. CONCLUSIONS: This experience and that reported in the literature suggest that it is frequently impossible to preserve the function of the nerve of origin with surgical treatment of cervical neurilemomas.

Adolescent↗

Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi.

Contractile and relaxant responses to capsaicin and resiniferatoxin were examined in human isolated bronchus (5-12 mm o.d.). Bronchi isolated from 10 of 16 lungs contracted in response to capsaicin. The contractions averaged 20% of maximal contraction at 1 microM and averaged > 40% maximal contraction at 300 microM (the highest concentration studied). The capsaicin-induced contractions were mimicked by resiniferatoxin (0.1-10 microM) and inhibited by the putative capsaicin receptor antagonist, capsazepine (10 microM). The contractile response to capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3 microM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin B (0.1 microM), substance P (1 microM), neuropeptide gamma (10 nM), and neuropeptide K (10 nM) which produced similar-size contractions were almost abolished by 0.1 microM SR 48968. The bronchi isolated from 8 of 16 lungs also exhibited relaxations in response to capsaicin. Capsaicin-induced relaxations were not inhibited by the nitric oxide synthase inhibitor L-nitro-n-arginine (10 microM). In whole-cell patch-clamp experiments on human cultured airway smooth muscle cells, capsaicin was found to enhance outward currents due to the activation of charybdotoxin-sensitive large conductance Ca2+-activated K+ channels. Neither the capsaicin-induced contractions nor the relaxations were mimicked by angiotensin II, bombesin, or calcitonin gene-related peptide at concentrations up to 1 microM. These results suggest that capsaicin and resiniferatoxin can alter smooth muscle tone, but this response does not appear to involve substance P or related neurokinins. Relaxations to capsaicin may, however, involve the activation of large conductance Ca2+-activated K+ channels.

Adult↗

Role of soluble guanylyl cyclase in the relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea and human bronchus.

The effect of the novel, selective, soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolol[4,3-a]quinoxalin-1-one (ODQ) on the nitric oxide component of the nonadrenergic, noncholinergic relaxation in guinea pig trachea was examined. Relaxant responses to field stimulation (1-16 Hz, 8 V, 1 ms for 15 s) in the presence of indomethacin (3 microM), atropine (1 microM), propranolol (1 microM), alpha-chymotrypsin (2 U/ml) and histamine (3 microM) were partially inhibited by 0.1 microM ODQ and almost abolished by 1 microM ODQ. In addition, relaxations to the nitric oxide donor 3-morpholinosyndnonimine-N-ethylcarbamide were partially inhibited by 0.1 microM ODQ and abolished by 1 microM ODQ. Relaxations to 3-morpholinosyndnonimine-N-ethylcarbamide in human bronchus were also substantially inhibited by ODQ (1-10 microM). By contrast, relaxations elicited by the stable 3',5'-cyclic monophosphate analog 8-bromoguanosine-3',5'-cyclic monophosphate and by isoproterenol were unaffected by 1 microM ODQ in guinea pig trachea and by 10 microM ODQ in human bronchus. These results suggest that relaxant responses to endogenously released or exogenously added nitric oxide in guinea pig trachea and human bronchus are mediated via the activation of soluble guanylyl cyclase and the formation of guanosine-3',5'-cyclic monophosphate.

Animals↗

Isolated lung perfusion with FUDR in the rat: pharmacokinetics and survival.

BACKGROUND: Although surgical resection remains the mainstay of treatment for metastatic pulmonary colorectal cancer, 5-year survival approaches only 30% to 40%. We have developed a model of isolated left lung perfusion (ILP) with FUDR (2'-deoxy-5-fluorouridine) for the treatment of pulmonary colorectal metastases. FUDR ILP toxicity and pharmacokinetics were evaluated and compared with continuous intravenous infusion in the rat. METHODS: Toxicity was first evaluated in F344 rats (n = 17) after left ILP (20-minute perfusion at 0.5 mL/min) with 21 mg/mL (n = 11), 28 mg/mL (n = 2), 35 mg/mL (n = 2), and 70 mg/mL (n = 2) of FUDR. Animals were followed up and weights recorded for 14 days postoperatively before a right pneumonectomy was performed to evaluate the effect of FUDR perfusion on left lung function. In the second study, 32 rats (n = 8/group) underwent: systemic FUDR (intravenous), or ILP with 7, 14, and 21 mg/mL respectively (ILP 7, ILP 14, and ILP 21 groups). Left lungs and serum were analyzed for FUDR and 5-fluorouracil by high-performance liquid chromatography. RESULTS: Rats perfused with doses of FUDR greater than 21 mg/mL died perioperatively. All animals perfused at 21 mg/mL survived until day 14, and 8/11 survived a right pneumonectomy. Rats that survived ILP resumed normal weight gain and grooming habits within 1 week. Pharmacokinetic evaluation demonstrated that ILP at 21 mg/mL maximally elevated total lung FUDR and 5-fluorouracil levels (508.5 +/- 96.4 micrograms/g lung) in comparison with the ILP 14, ILP 7, and intravenous groups (299.1 +/- 44.8, 116.0 +/- 21.1, and 7.5 +/- 4.1 micrograms/g lung, respectively) (p < 0.05). Serum FUDR levels were 10.5 +/- 6.8, 1.3 +/- 0.5, 2.31 +/- 1.1, and 1.2 +/- 0.4 microgram/g lung (p = not significant) for intravenous, ILP 7, ILP 14, and ILP 21 groups, respectively. CONCLUSIONS: Isolated left lung perfusion with FUDR is well tolerated to a maximum dose of 21 mg/mL and results in significantly higher FUDR and 5-fluorouracil lung levels with low serum levels compared with intravenous treatment. These higher pulmonary levels may offer advantages in the treatment of pulmonary colorectal metastases.

Animals↗

Prejunctional inhibition of cholinergic responses by prostaglandin E2 in human bronchi.

The effect of prostaglandin E2 (PGE2) on cholinergic responses elicited by electrical field stimulation (EFS) (8 Hz, 1 ms, 8 V for 10 s every 100 s) of human isolated human bronchi was studied. Indomethacin (1 microM) was found to produce approximately a 100% increase in the cholinergic response. In the presence of indomethacin, PGE2 (1-300 nM) was found to concentration-dependently inhibit the cholinergic responses to EFS. A maximal inhibition was obtained with 100 nM PGE2 which produced an 80% inhibition of the cholinergic response. By contrast 100 nM PGE2 was without significant effect on the concentration response curve to exogenously added acetylcholine. The inhibitory effect of PGE2 on the EFS-induced cholinergic responses was not modified by the large conductance Ca(2+)-activated K+ channel inhibitor charybdotoxin (100 nM). These results suggest that endogenously released prostaglandins, presumably PGE2, act to inhibit cholinergic responses by a prejunctional mechanism in human isolated bronchi. In contrast to other autocoids, this inhibition does not involve the activation of large-conductance Ca(2+)-activated K+ channels.

Acetylcholine↗

Inhibition by zinc protoporphyrin-IX of vasoactive intestinal peptide-induced relaxations of guinea pig isolated trachea.

Carbon monoxide, formed as a product of heme oxygenase activity, has been postulated to act as an intra- and intercellular messenger molecule. We addressed the hypothesis that heme oxygenase is involved in the relaxation of the guinea pig trachealis elicited by vasoactive intestinal peptide (VIP) or by electrical field stimulation. Immunohistochemical studies revealed the presence of heme oxygenase-II in airway smooth muscle and epithelium. Zinc protoporphyrin-IX (ZnPPn), an inhibitor of heme oxygenase, effectively inhibited VIP-induced relaxations of tracheal smooth muscle. Surprisingly, the potency of ZnPPn was increased if the drug was preincubated with the VIP solution before addition to the tissue bath. The relaxant responses to 3-morpholinosydnonimine were unaffected by ZnPPn. Zinc deuteroporphyrin-IX 2,4 bisglycol, a more potent inhibitor of heme oxygenase than ZnPPn, did not affect the VIP responses. ZnPPn (300 microM) had no effect on nonadrenergic, noncholinergic relaxations of the guinea pig trachea. These data indicate that although ZnPPn is an efficacous inhibitor of VIP-induced relaxations of the guinea pig trachealis, it is unlikely that heme oxygenase plays an important role in this response. Rather, the data are consistent with the hypothesis that ZnPPn inhibits the VIP response via an interaction with the VIP molecules themselves. Although the results demonstrate the existence of heme oxygenase-II in the guinea pig trachealis, they do not support the hypothesis that it plays a role in electrical field stimulation-induced nonadrenergic, noncholinergic relaxations.

Animals↗

Isolated lung perfusion with FUDR is an effective treatment for colorectal adenocarcinoma lung metastases in rats.

Currently, the only treatment capable of significantly prolonging survival in patients with isolated pulmonary metastases from colorectal adenocarcinoma is complete resection. Systemic chemotherapy has been shown to provide little benefit. We evaluated the efficacy of highdose, organ-specific 2'-deoxy-5-fluorouridine (FUDR) using a model of isolated single-lung perfusion (ILP) in the rat. On day 0, 28 BDIX rats were inoculated intravenously with 10(6) viable Sp-5 colorectal adenocarcinoma cells. On day 10 after-tumor inoculation, animals were randomized into five treatment groups. Group I received a continuous intravenous infusion of FUDR (1 mg.kg-1.d-1) for 7 days administered by an osmotic minipump. Group II underwent isolated left lung perfusion with a buffered Hespan solution, groups III to V underwent ILP with 3.5, 7, and 14 mg of FUDR per milliliter of the buffered Hespan solution, respectively. Animals undergoing ILP were anesthetized with pentobarbital, intubated, and ventilated, and then underwent left thoracotomy with cannulation of the pulmonary artery; the pulmonary artery and vein were clamped proximally. Groups II to V were perfused for 20 minutes at a rate of 1 mL/min, followed by a 5-minute washout with FUDR-free buffered Hespan solution. On day 26 after tumor inoculation, the animals in all groups were sacrificed and their lungs were stained and counted. Animals that underwent ILP with 14 mg of FUDR per milliliter of the buffered Hespan solution showed a significant decrease in the number of tumor nodules on the treated side versus the number on the untreated side (455.2 +/- 87.3 versus 11 +/- 6.4; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Neurokinin receptors subserving bronchoconstriction.

Tachykinin receptor subtypes were initially defined using agonist potency rations for the endogenous ligands substance P (SP), neurokinin (NK) A, and NKB. On this basis it was suggested that there are three tachykinin receptor subtypes. These subtypes were designated NK1, NK2, and NK3, where SP is most potent at NK1 receptors, NKA is most potent at NK2 receptors, and NKB is most potent at NK3 receptors. Recently analogs of the endogenous ligands that show greater selectivity (about 1000-fold) for the different receptor subtype have been developed. In addition selective antagonists, which are either nonpeptides or modified peptides, for the receptor subtypes have been developed. This minireview concentrates on the wealth of new knowledge concerning the tachykinin receptor subtypes subserving bronchoconstriction in several mammalian species, including man, provided by the use of these selective agonists and antagonists.

Animals↗

Pharmacological characterization of a new class of nonpeptide neurokinin A antagonists that demonstrate species selectivity.

We examined the pharmacology of ZM253,270 and two representative examples of the pyrrolopyrimidines, a new class of nonpeptide, NK-2 receptor (NK-2R) antagonists. ZM253,270 competitively inhibited [3H]NKA binding to native or cloned NK-2R from hamster urinary bladder (Ki = 2 nM), but was a weaker (48-fold) inhibitor of [3H]NKA binding to cloned human NK-2R. A similar species selectivity was observed with less potent analogs of ZM253,270. The pyrrolopyrimidines demonstrated only marginal inhibition of [3H]SP binding to NK-1R in guinea pig lung membranes (Ki > 2 microM). In hamster trachea, ZM253,270 competitively antagonized the contractile response evoked by neurokinin A (NKA, -logKB = 7.5). In human bronchus, ZM253,270 was about 90-fold less potent as a competitive antagonist of NKA. The data from ligand binding assays in cloned receptors combined with functional receptor assays in airway smooth muscles, demonstrate that the nonpeptide antagonist ZM253,270 is selective for the NK2 receptor species that are prevalent in hamster, compared with those found in human tissues.

Animals↗

Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea.

Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 8 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and treated with alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The effect of the phosphodiesterase (PDE) isozyme selective inhibitors siguazodan (PDE III-selective), rolipram (PDE IV-selective), denbufylline (PDE IV-selective) and zaprinast (PDE V-selective) was examined on the relaxant responses to field stimulation and on relaxations elicited by the nitric oxide donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1). The response to field stimulation in the presence of alpha-chymotrypsin (the putative nitric oxide component), at all the frequencies tested, was potentiated significantly by the PDE IV inhibitors rolipram (1 and 10 microM) and denbufylline (3 and 10 microM) as were responses to SIN-1. The PDE V inhibitor zaprinast (30 microM) potentiated relaxations elicited by field stimulation at 8 and 16 Hz and also potentiated responses to SIN-1. The PDE III inhibitor siguazodan (1 microM), however, was without effect on relaxant responses to field stimulation or to SIN-1. These results suggest that the nitric oxide component of the nonadrenergic, noncholinergic relaxant response is mediated primarily via cyclic AMP whose action is inactivated by a PDE IV isozyme and also by cyclic GMP which is inactivated by a PDE V isozyme.

3',5'-Cyclic-AMP Phosphodiesterases↗

Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi.

The intrinsic isometric tone of human isolated intralobar bronchi was evaluated in vitro. Human bronchi (inner diameter, 3 to 12 mm) were obtained from patients undergoing lung resection and from organ donors. The organ donor tissue was studied approximately 24 h after resection, during which time it was shipped to the laboratory in RPMI 1640 medium at 4 degrees C. The bronchi obtained from patients with cancer was placed in the same medium and studied within 4 h of resection. All tissues were suspended in 10-ml organ baths containing oxygenated Krebs' solution at 37 degrees C, at an initial load of 2 g. Tissues were washed every 15 min until they exhibited a stable tension (usually 60 min). Under these conditions the amount of active tension in the bronchi studied on the day of resection averaged 65 +/- 9% of the maximal response to BaCl2 (30 mM), whereas after overnight incubation it averaged 31 +/- 6%. Neither indomethacin nor atropine influenced the intrinsic tone in these tissues. By contrast, the LTD4 antagonists SKF 104353 and ICI 198615 and the histamine H-1 antagonists pyrilamine and chlorpheniramine effectively relaxed the bronchi. The 5' lipoxygenase inhibitor zileuton also produced a small fall in tension. Studies in which pyrilamine was combined with the leukotriene receptor antagonists indicated an additive effect. These results indicate that human bronchial smooth muscle exhibits a high degree of intrinsic tone, averaging more than 50% of available tone in fresh tissues studied in vitro under isometric conditions. The results suggest that this tone is due to the continual production and release of histamine and cysteinyl-leukotrienes.

Bronchi↗

Ragweed antigen E and anti-IgE in human central versus peripheral isolated bronchi.

The ability of antigen to contract passively sensitized tissues was examined in human central (5 to 12 mm) and peripheral (0.5 to 2 mm) bronchi. Both central and peripheral bronchi contracted to ragweed antigen E (RW AgE), and these contractions were virtually abolished by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. There were, however, quantitative differences in contractile responses and in mediator release to RW AgE between central and peripheral bronchi. RW AgE was approximately 20-fold more potent in contracting peripheral bronchi compared with central bronchi. On a per weight of tissue basis, RW AgE released six-fold more histamine, 15- to 20-fold more immunoreactive leukotriene D4 (i-LTD4) and two- to 10-fold more prostanoids in the peripheral bronchi compared with central bronchi. Anti-IgE mimicked the effect of RW AgE with respect to inflammatory mediator release and with respect to the magnitude of the contractile response in peripheral and central bronchi. Anti-IgE, however, was more potent in contracting central than peripheral bronchi. Moreover, in peripheral bronchi, contractile responses to anti-IgE were only partially inhibited by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. These results indicate that the qualitative characteristics of antigen-induced mediator release and muscle contraction are similar in central versus peripheral bronchi. However, RW AgE is much more potent in causing smooth muscle constriction, and is capable of releasing a greater quantity of inflammatory mediators in peripheral bronchi/bronchioles than in the more central bronchi.

Adult↗