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Biomedical subjects

J Carroll

Publications and source records attributed to J Carroll.

At least 19 recordsLinked to original sources
PubMed1998

The ketogenic diet: a practical guide for caregivers.

The ketogenic diet is a high-fat, low-carbohydrate diet that results in ketosis. It has been in use for nearly 70 years. Several modifications of the diet's original form, including the medium-chain triglyceride (MCT) diet, have been made in an attempt to overcome the obstacles of compliance and acceptance, which have been critical factors in determining its success. The practical guide for caregivers that is presented here uses elements of both the original ketogenic diet and the MCT diet, with added ideas. Our modified diet has been in use for more than 3 years at Columbia Presbyterian Medical Center Babies and Children's Hospital of New York. The majority of parents and children find our diet more acceptable and/or more user friendly than other types of ketogenic diets. Thus, compliance is better. The variety of foods offered is greater and provides a more normal diet than the other types of ketogenic diets. In addition, the calculations for nutritionists are easier, and parents are able to adjust the diet without the fear that their child will lose ketones.

Child↗
PubMed1997

In vivo homologous regulation of mu-opioid receptor gene expression in the mouse.

Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in rats and mice following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possibility that in vivo homologous regulation by agonists may not occur. Therefore, in the present study, the effect of a high intrinsic efficacy opioid receptor agonist on opioid receptor density, gene expression and tolerance was determined. Mice were infused with etorphine for 7 days using an osmotic minipump, then the pump was removed and studies conducted 16-168 h later. Etorphine (50-250 microg/kg/day) infusion produced significant dose-dependent tolerance to the analgesic (tailflick) effects of etorphine, as well as dose-dependent mu-opioid receptor downregulation in brain at 16 h following the end of the infusion. Mu-opioid receptor density returned to control levels over a 168 h period following the end of etorphine (250 microg/kg/day) infusion. Similarly, the magnitude of tolerance decreased over the same period. Evaluation of changes in brain mu-opioid receptor mRNA 16 h following etorphine infusion indicated that there was dose-dependent increase in steady-state levels, with no significant change in GAPDH mRNA. The increase in mu-opioid receptor mRNA was approximately 55-65% over control at the highest etorphine infusion dose. Mu-opioid receptor mRNA returned to control levels over a 168 h period following the end of etorphine (250 microg/kg/day) infusion. These data suggest that the increase in mu-opioid receptor mRNA following the termination of etorphine treatment may drive the recovery of mu-opioid receptors. These data are the first demonstration of in vivo homologous regulation of mu-opioid receptor gene expression in the mouse by an opioid receptor agonist that produces tolerance and receptor downregulation.

Analgesics, Opioid↗
PubMed1997

The effect of in vivo ethanol consumption on cyclic AMP and delta-opioid receptors in mouse striatum.

In this study the effect of in vivo ethanol consumption on cyclic AMP (cAMP) and [D-Ala2,D-Leu5]enkephalin (DADLE) inhibition of forskolin-stimulated cAMP production was examined in mouse striatum. Effects of ethanol on striatal delta-opioid receptor (DOR) density and mRNA were also examined. Mice had unlimited access to 7% (v/v) ethanol alone or water for 1 or 7 days and were then sacrificed and striatum removed for analysis. There was no difference in basal cAMP formation between water and ethanol-treated mouse striatum following 7 day treatment, and a small, but statistically significant increase in basal cAMP in the ethanol group following 1 day treatment. Both 1 day and 7 day ethanol treatment did not significantly alter the percentage increase in cAMP following treatment with 10 microM forskolin. There was a significant effect of ethanol treatment on the maximum inhibitory effect of DADLE on forskolin-stimulated cAMP formation following both 1 and 7 day ethanol treatment. The DADLE IC50 was unaffected by ethanol treatment. Saturation binding studies ([3H]Deltorphin II) indicated no effect of ethanol on Bmax or Kd in striatum. Similarly, no difference between water and ethanol-treated was observed for DOR mRNA in striatum. These data indicate that ethanol consumption can alter opioid regulation of cAMP formation. However, this effect is not related to changes in any delta-opioid receptor parameters that were examined.

Animals↗
PubMed1997

Tumor induction by a transformation-defective polyoma virus mutant blocked in signaling through Shc.

Transformation of cells in culture by polyoma virus requires integration of signals downstream of middle T-Shc and middle T-phosphatidylinositol 3-kinase interactions, but the same is not true for induction of tumors in the mouse. Thus, a middle T mutant defective in transformation and blocked in binding Shc is able to induce a broad spectrum of tumors after inoculation into newborn mice. The "tumor profile" induced by the mutant shows enhancement of tumors at some sites and reductions at others but otherwise resembles that induced by the wild-type virus. A nontransforming double-mutant blocked in binding phosphatidylinositol 3-kinase as well as Shc is severely affected but still induces some tumors. These results show that pathways that must cooperate to induce full transformation of cells in vitro can act independently and are to a large extent redundant in tumor induction.

3T3 Cells↗
PubMed1997

Analysis of the large aqueous pores produced by a Bacillus thuringiensis protein insecticide in Manduca sexta midgut-brush-border-membrane vesicles.

An osmotic swelling assay utilising carboxyfluorescein self-quenching to measure intravesicular volume changes was adapted to investigate permeability changes induced by the Bacillus thuringiensis Cry1Ac delta-endotoxin in Manduca sexta midgut-brush-border-membrane vesicles (BBMV). This assay provides a more quantitative analysis of Cry-toxin-induced BBMV permeability changes, extending our previously published protocol which employed a light-scattering signal to monitor delta-endotoxin activity [Carroll, J. & Ellar, D. J. (1993) Eur. J. Biochem. 214, 771-778]. The fluorescence signal changes, supported by electron microscopy of the BBMV, demonstrated that Cry1Ac altered the membrane permeability for large non-electrolyte solutes. With this approach Cry1Ac was observed to induce or form pores freely permeant for raffinose (1.14 nm diameter) and using non-electrolytes of increasing size the pores were estimated to have a limiting diameter of approximately 2.4-2.6 nm under alkaline pH conditions.

Animals↗
PubMed1997

Intramolecular proteolytic cleavage of Bacillus thuringiensis Cry3A delta-endotoxin may facilitate its coleopteran toxicity.

The Cry3A delta-endotoxin protein inclusion synthesized by Bacillus thuringiensis subsp. tenebrionis is soluble in alkaline and acid buffer solutions but the toxin precipitates when returned to neutral pH conditions. The midgut pH of susceptible beetle larvae is neutral to slightly acidic, a pH environment in which the Cry3A toxin is insoluble. To investigate this paradox we studied the Cry3A toxin after various proteolytic treatments. In many cases the toxin was cleaved into polypeptides that remained associated under non-denaturing conditions. Interestingly a chymotrypsinized Cry3A product was soluble under neutral pH conditions, retained full activity against susceptible beetle larvae, and exhibited specific binding to Leptinotarsa decemlineata midgut membranes.

Animals↗
PubMed1997

The effect of mu-opioid receptor antisense on morphine potency and antagonist-induced supersensitivity and receptor upregulation.

The present study examined the effect of in vivo antisense oligodeoxynucleotide treatment on naltrexone (NTX)-induced functional supersensitivity and mu-opioid receptor up-regulation in mice. On day 1 mice were implanted S.C. with a NTX or placebo pellet and injected I.T. and I.C.V. with dH2O or oligodeoxynucleotides. The oligodeoxynucleotides were designed so that they were either perfectly complementary to the first 18 bases of the coding region of mouse mu-opioid receptor mRNA, or had one (Mismatch-1) or four (Mismatch-4) mismatches. On days 3, 5, 7, and 9, mice were again injected I.T. and I.C.V. with dH2O or one of the oligodeoxynucleotides. After the final injections on day 9, placebo and NTX pellets were removed, and 24 h later mice were tested for morphine analgesia or sacrificed for saturation binding studies ([3H]DAMGO). Naltrexone increased the analgesic potency of morphine in dH2O treated mice by approximately 70%. In binding studies, NTX significantly increased density of brain (approximately 60%) and spinal cord (approximately 140%) mu-opioid receptors without affecting affinity. The mu-opioid antisense and the oligodeoxynucleotide with one mismatch (Mismatch-1) significantly reduced the potency of morphine by approximately twofold in placebo-treated mice. The oligodeoxynucleotide with four mismatches (Mismatch-4) did not significantly alter morphine potency. When placebo-treated mice were treated with either the antisense to the mouse mu-opioid receptor, Mismatch-4 or Mismatch-1 there were no significant changes in the density of mu-opioid receptors. Thus, mu-opioid antisense significantly reduced morphine potency without changing mu-opioid receptor density. When NTX and oligodeoxynucleotide treatments were combined, there was no change in NTX-induced supersensitivity and mu-opioid receptor upregulation. These data suggest that opioid antagonist-induced supersensitivity and upregulation of mu-opioid receptors does not involve changes in gene expression.

Animals↗
PubMed1997

The Bacillus thuringiensis Cry1Ac toxin-induced permeability change in Manduca sexta midgut brush border membrane vesicles proceeds by more than one mechanism.

Aminopeptidase N purified from whole Manduca sexta midgut binds the Cry1Ac insecticidal toxin from Bacillus thuringiensis and this binding is inhibited by N-acetylgalactosamine (GalNAc). We have examined the membrane permeabilising activity of the Cry1Ac toxin using brush border membrane vesicles (BBMV) prepared from the anterior (A-BBMV) and posterior (P-BBMV) subregions of the M. sexta midgut. A toxin mixing assay demonstrated a faster rate of toxin activity on P-BBMV than on A-BBMV. In the presence of GalNAc this rapid activity on P-BBMV was reduced to the rate seen with A-BBMV. GalNAc had no effect on the rate of A-BBMV permeabilisation by Cry1Ac. Aminopeptidase N assays of A- and P-BBMV demonstrated that this Cry1Ac binding protein is concentrated in the posterior midgut region of M. sexta. It therefore appears that there are two mechanisms by which Cry1Ac permeabilises the M. sexta midgut membrane: a GalNAc-sensitive mechanism restricted to the posterior midgut region, probably involving aminopeptidase N binding, and a previously undetected mechanism found in both the posterior and anterior regions.

Animals↗
PubMed1996

E-selectin expression on human brain microvascular endothelial cells.

E-Selectin is an endothelial adhesion molecule involved in binding and targeting of neutrophils. Little is known of its expression in the brain. We examined the expression of E-selectin on cultured human brain microvascular endothelial cells (HBMEC). There was no basal expression of E-selectin on HBMEC but with I1-1b, tumor necrosis factor (TNF), or lipopolysaccharide (LPS) stimulation there was surface expression at 4 h. The expression was quantitatively less than on cultured human umbilical vein endothelial cells (HUVEC). The cytokine-induced upregulation was partially inhibited with the glutathione donor, N-acetylcysteine (NAC), the free radical scavenger, dimethylthiourea (DMTU; 15 mM) and dexamethasone (1 microM). Allopurinol (100 microM) had no effect. TNF activated nuclear factor kappa B (NF kappa B) in HBMEC. This activation could be attenuated by prior treatment with NAC and dexamethasone. Thiol donors and corticosteroids could play a role in inhibiting potentially deleterious neutrophil-endothelial interactions in inflammatory conditions involving the brain.

Allopurinol↗
PubMed1996

Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: a prospective randomized controlled trial.

INTRODUCTION: We undertook a prospective, randomized, controlled clinical trial to evaluate morbidity outcomes and safety of a modified anesthetic technique to provide shorter sedation and early extubation (1 to 6 hours) than those of the conventional anesthetic protocol used for prolonged sedation and extubation (12 to 22 hours) in patients after coronary artery bypass grafting. METHODS: One hundred twenty patients undergoing elective coronary artery bypass grafting were prospectively assigned randomly to either an early extubation group (n = 60; 15 micrograms.kg-1 fentanyl and 2 to 6 mg.kg-1.hour-1 propofol and isoflurane) or to a conventional extubation group (n = 60; 50 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 midazolam and isoflurane). Cardiac morbidity (postoperative myocardial ischemia, postoperative myocardial infarction, and perioperative sympathoadrenal stress response), respiratory morbidity (postextubation apnea, alveolar-arterial oxygen gradient, pulmonary shunting, oxygen consumption, atelectasis, and reintubation), hemodynamic values and vasoactive medication requirements, intraoperative awareness, postoperative cognitive function, 30 day mortality, and intensive care unit and hospital lengths of stay were compared between the two groups. RESULTS: Fifty-one of the 60 patients in each group (85%) were extubated within the defined time period. Postoperative extubation time and intensive care unit and hospital lengths of stay were significantly shorter in the early group. At 48 hours after operation, there were no significant differences between the two groups in myocardial ischemia incidences, ischemia burdens, or creatine kinase isoenzyme MB levels. Four patients in the conventional group, but not in the early group, had postoperative myocardial infaction. The extubation anesthetics used were effective in suppressing the perioperative plasma catecholamine stress response in both groups. Postextubation apnea characteristics were similar between the groups. Intrapulmonary shunt fraction improved significantly in the early group at 4 hours after extubation. The incidences and degree of atelectasis did not differ significantly between the two groups. The incidences of treated postoperative complications were comparable between the two groups, but three patients in the conventional group died as a result of stroke or postoperative myocardial infarction. CONCLUSION: Early extubation after coronary artery bypass grafting is safe and does not increase perioperative morbidity. There is an improvement in postextubation intrapulmonary shunt fraction and a reduction in intensive care unit and hospital lengths of stay.

Aged↗
PubMed1996

Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse.

In mammals, the maternal and paternal genomes are required for embryonic development. This is due to genomic imprinting which leads to the expression or repression of genes solely on the basis of the parent from which they were inherited. As a result, parthenogenetic embryos die before day 10 of gestation and show limited development of extra-embryonic membranes. Maternal imprinting is established during oogenesis and is associated with allele specific modifications in DNA methylation. We have investigated epigenetic modifications during oocyte growth using nuclear transfer techniques to produce mature oocytes with maternal chromatin derived from non-growing oocytes. Parthenogenetic activation of such oocytes leads to the development of normal size fetuses with a well developed placenta on day 13.5 of gestation; three days further than previously recorded for parthenogenetic development. In contrast, after fertilization, only one embryo was recovered on 9.5 days of gestation. Further, in these embryos we investigated the well characterized methylation pattern of the maternally expressed insulin-like growth factor II receptor gene (Igf2r) and found that the pattern of methylation was indeed different to that of fertilized control embryos. Thus, the embryonic phenotypes observed here correlate with changes in epigenetic events that normally occur during oocyte growth.

Animals↗
PubMed1996

A cell cycle-associated change in Ca2+ releasing activity leads to the generation of Ca2+ transients in mouse embryos during the first mitotic division.

We have used Ca2+-sensitive fluorescent dyes to monitor intracellular Ca2+ during mitosis in one-cell mouse embryos. We find that fertilized embryos generate Ca2+ transients at nuclear envelope breakdown (NEBD) and during mitosis. In addition, fertilized embryos arrested in metaphase using colcemid continue to generate Ca2+ transients. In contrast, parthenogenetic embryos produced by a 2-h exposure to strontium containing medium do not generate detectable Ca2+ transients at NEBD or in mitosis. However, when parthenogenetic embryos are cultured continuously in strontium containing medium Ca2+ transients are detected in mitosis but not in interphase. This suggests that mitotic Ca2+ transients are detected in the presence of an appropriate stimulus such as fertilization or strontium. The Ca2+ transient detected in fertilized embryos is not necessary for inducing NEBD since parthenogenetic embryos undergo nuclear envelope breakdown (NEBD). Also the first sign that NEBD is imminent occurs several minutes before the Ca2+ transient. The Ca2+ transient at NEBD appears to be associated with the nucleus since nuclear transfer experiments show that the presence of a karyoplast from a fertilized embryo is essential. Finally, we show that the intracellular Ca2+ chelator Bapta inhibits NEBD in fertilized and parthenogenetic embryos in a dose-dependent manner. These studies show that during mitosis there is an endogenous increase in Ca2+ releasing activity that leads to the generation of Ca2+ transients specifically during mitosis. The ability of Ca2+ buffers to inhibit NEBD regardless of the presence of global Ca2+ transients suggests that the underlying cell cycle-associated Ca2+ releasing activity may take the form of localized Ca2+ transients.

Animals↗
PubMed1996

Early tracheal extubation after coronary artery bypass graft surgery reduces costs and improves resource use. A prospective, randomized, controlled trial.

BACKGROUND: Economics has caused the trend of early tracheal extubation after cardiac surgery, yet no prospective randomized study has directly validated that early tracheal extubation anesthetic management decreases costs when compared with late extubation after cardiac surgery. METHODS: This prospective, randomized, controlled clinical trial was designed to evaluate the cost savings of early (1-6 h) versus late tracheal extubation (12-22 h) in patients after coronary artery bypass graft (CABG) surgery. The total cost for the services provided for each patient was determined for both the early and late groups from hospital admission to discharge home. All costs applicable to each of the services were classified into direct variables, direct fixed costs, and overhead (an indirect cost). Physician fees and heart catheterization costs were included. The total service cost was the sum of unit workload and overhead costs. RESULTS: One hundred patients having elective CABG who were younger than 75 yr were studied. Including all complications, early extubation (n = 50) significantly reduced cardiovascular intensive care unit (CVICU) costs by 53% (P < 0.026) and the total CABG surgery cost by 25% (P < 0.019) when compared with late extubation (n = 50). Forty-one patients (82%) in each group were tracheally extubated within the defined period. In the early extubation group, the actual departmental cost savings in CVICU nursing and supplies was 23% (P < 0.005), in ward nursing and supplies was 11% (P < 0.05), and in respiratory therapy was 12% (P < 0.05). The total cost savings per patient having CABG was 9% (P < 0.001). Further cost savings using discharge criteria were 51% for CVICU nursing and supplies (P < 0.001), 9% for ward nursing and supplies (P < 0.05), and 29% for respiratory therapy (P < 0.001), for a total cost savings per patient of 13% (P < 0.001). Early extubation also reduced elective case cancellations (P < 0.002) without any increase in the number of postoperative complications and readmissions. CONCLUSIONS: Early tracheal extubation anesthetic management reduces total costs per CABG surgery by 25%, predominantly in nursing and in CVICU costs. Early extubation reduces CVICU and hospital length of stay but does not increase the rate or costs of complications when compared with patients in the late extubation group. It shifts the high CVICU costs to the lower ward costs. Early extubation also improves resource use after cardiac surgery when compared with late extubation.

Aged↗
PubMed1996

Aldosterone-producing adenomas do not contain glucocorticoid-remediable aldosteronism chimeric gene duplications.

In glucocorticoid-remediable aldosteronism (GRA) a chimeric gene has been described with the activity of aldosterone synthase, but the promoter of 11 beta-hydroxylase leading to ectopic expression of aldosterone synthase activity in the zona fasciculata. Similar to GRA, in aldosterone-producing adenomas (APA), the primary regulation of aldosterone production is ACTH, and there is increased production of the 18-oxygenated cortisol compounds, 18-oxocortisol and 18-hydroxycortisol. Because of these hormonal similarities, we tested whether a chimeric GRA-like gene was present in APA from 11 patients. A GRA-like chimeric gene was not found in the DNA from these tumors and, therefore, is not the mechanism responsible for hyperaldosteronism in APA.

Adenoma↗
PubMed1996

Ca2+ release and the development of Ca2+ release mechanisms during oocyte maturation: a prelude to fertilization.

Oogenesis involves the production of an oocyte that can undergo fertilization and support early development. The stimulus that initiates embryogenesis is an increase in the concentration of intracellular Ca2+ in the cytoplasm of the oocyte at the time of fertilization. The development of the ability of the oocyte to release Ca2+ in response to the fertilizing spermatozoon is an essential step in the process of oogenesis. Mammalian oocytes are particularly useful for studying the development of Ca2+ signalling systems, owing to the series of Ca2+ oscillations generated at fertilization, compared with the monotonic Ca2+ increase seen in nonmammalian species. Recent evidence has revealed that Ca2+ release mechanisms are modified during oogenesis. The maximal sensitivity of Ca2+ release is reached in the final stages of oocyte maturation, just before the optimal time for fertilization. In this review, we consider the mechanism underlying Ca2+ release in mammalian oocytes and discuss how the release mechanisms are modified during oocyte maturation. The tight co-ordination of the differentiation of the Ca2+ signalling system with the development of the oocyte provides a means of ensuring successful activation at the time of fertilization. Finally, we consider the consequences for embryo development in circumstances in which the co-ordination is lost.

Animals↗
PubMed1996

Attitudes to drug users according to age of staff.

The attitudes of professionals working with intravenous drug users, and their perceptions of service delivery, are likely to be affected by age. Younger professionals tend to be more positive in their attitudes towards intravenous drug users. Older professionals tend to be less concerned about the risks from HIV infection than younger ones. More research is needed into the effects of age group on attitudes.

Adult↗
PubMed1996

Attitudes to drug users according to staff grade.

The attitudes of professionals working with intravenous drug users are likely to be affected by clinical grade. Perceptions of service delivery to intravenous drug users are likely to be affected by status. Senior professionals tend to be more positive in their attitudes towards intravenous drug users. Attitudes and perceptions of service delivery are very important in determining the standard of care delivery.

Adult↗