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Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 235 records · Page 13Linked to original sources
PubMed1995

The rabbit as a model for studies of cocaine exposure in utero.

The rabbit has been used to model the potential effects of in utero exposure to cocaine on fetal and postnatal development. Special advantages of this animal model include the fact that cocaine can be easily administered intravenously, thus mimicking crack cocaine use by pregnant women. Results indicate that at the dosage used (8 mg/kg of body weight, given intravenously daily) gross teratologic defects do not develop. Cocaine-exposed pregnant does not differ from controls in weight gain or in the number of live kits delivered. Cocaine-exposed kits do not differ from controls in survival or in postnatal weight gain. The importance of this rabbit model is that offspring that have been exposed to these doses of cocaine in utero have a variety of abnormalities in structure and function of the central nervous system in the absence of any major teratologic defects.

Abnormalities, Drug-Induced↗
PubMed1995

Home parenteral nutrition: the Royal Prince Alfred Hospital experience.

This paper reviews the outcomes for 14 patients treated with long-term home parenteral nutrition at the Royal Prince Alfred Hospital between 1978 and 1994. Prior to the introduction of home parenteral nutrition, all patients were unable to maintain adequate nutrition by enteral means and all had experienced repeated and/or long term admissions to hospital for total parenteral nutrition. The median time patients had been on home parenteral nutrition was 468 days (range 7 days to 5,352 days) and seven patients were on home parenteral nutrition at the time of the review. The majority of patients were able to resume a reasonable place in society for varying periods and four of the patients returned to work. The conclusion from the Royal Prince Alfred experience is that home parenteral nutrition is a cost-effective method of maintaining nutrition in selected patients with chronic intestinal failure.

Adult↗
PubMed1995

The development and implementation of a quality assurance Master Audit Plan.

As a quality assurance (QA) department for a clinical research organization, QA conducts audit activities for clinical trials managed by our organization and acts as an independent QA group for several other companies. A quality assurance/regulatory compliance Master Audit Plan is developed for each study or each audit if the audit is an independent task. The Master Audit Plan designed for a specific clinical study consists of a combination of several QA activities designed to ensure quality and regulatory compliance, to define timelines, and to identify personnel. These activities may include the review of the regulatory documents for each investigative site prior to the shipping of test article (test article release), review of informed consent, review of internal sponsor study files, and clinical site audits. Results of audit activities conducted under the Master Audit Plan for several clinical studies have been compiled for three of the major QA tasks. These include test article release, informed consent review, and site audits. A review of regulatory document files for test article release indicated that 13% required additional documents or correction of submitted documents. A review of informed consents found that 32% required revision. Site audit activities indicated that the clinical sites were, in general, adhering to Federal regulations and GCP guidelines. Observations noted at sites tended to fall into the categories of test article accountability issues, regulatory document additions or revisions, and quality control issues.

Facility Regulation and Control↗
PubMed1994

2'-hydroxy-5,9-dimethyl-2-(3-methyl-2-butenyl)-6,7-benzomorphan (pentazocine) hydrochloride hydrate.

The title compound [1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano- 3- benzazocin-8-ol hydrochloride hydrate, C19H28NO+.-Cl-.1/8H2O, (I)] crystallizes with two molecules per asymmetric unit. A comparison of the bond lengths and torsion angles shows a side-chain orientation similar to that of cyclazocine but unlike that of naloxone. The two molecules are linked through a hydrogen-bond network to the interlayer Cl ions, forming a linear chain extending along the ac diagonal of the unit cell.

Crystallography, X-Ray↗
PubMed1994

Beta 2-adrenergic receptor-stimulated increase in cAMP in rat heart cells is not coupled to changes in Ca2+ dynamics, contractility, or phospholamban phosphorylation.

Previous studies have shown that both beta 1- and beta 2-adrenergic receptors (AR) are present in rat ventricular myocytes, but stimulation of these receptor subtypes elicits qualitatively different cellular responses (Xiao, R.-P., and Lakatta, E. G. (1993) Circ. Res. 73, 286-300). In the present study, the biochemical mechanism underlying the distinct beta AR subtype actions have been investigated. Although both beta 1AR and beta 2AR stimulation increased total cellular cAMP in suspensions of rat ventricular myocytes to a similar extent, the maximum elevation of the membrane bound cAMP by beta 2AR stimulation was only half of that induced by beta 1AR stimulation, suggesting that stimulation the beta AR subtypes leads to different compartmentation of cAMP. The effects of beta 1AR stimulation on Ca2+ transient (indexed by the transient increase in indo-1 fluorescence ration after excitation) and contraction amplitude (measured via photodiode array) and their kinetics closely paralleled the increase in cAMP. In contrast, the increase in both membrane bound and total cAMP content after beta 2AR stimulation were completely dissociated from the effects of beta 2AR stimulation to increase the amplitudes of cytosolic Ca2+ transient and contraction. Furthermore, beta 2AR stimulation did not phosphorylate phospholamban to the same extent as did beta 1AR stimulation. This finding provides a mechanism for the failure of beta 2AR stimulation to accelerate the kinetics of the Ca2+i (cytosolic Ca2+) transient and contraction. These results indicate that the effects of beta 2AR stimulation on Ca2+i transient and contraction are uncoupled from the cAMP production and cAMP-dependent protein phosphorylation and indicate that, in addition to coupling to adenylate cyclase, beta 2AR stimulation also activates other signal transduction pathway(s) to produce changes in cytosolic Ca2+ and contraction.

Animals↗
PubMed1994

Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation.

Most cells of the dorsal epidermis exit from the mitotic cycle after division 16 in Drosophila embryogenesis. This exit is dependent on the down-regulation of Drosophila cyclin E (DmcycE) during the final mitotic cycle. Ectopic expression of DmcycE after the final mitosis induces entry into S phase and reaccumulation of G2 cyclins and results in progression through a complete additional cell cycle. Conversely, analyses in DmcycE mutant embryos indicate that cyclin E is required for progression through S phase of the mitotic cycle. Moreover, endoreplication, which occurs in late wild-type embryos in the same pattern as DmcycE expression, is not observed in the mutant embryos. Therefore, Drosophila cyclin E, which forms a complex with the Dmcdc2c kinase, controls progression through S phase and its down-regulation limits embryonic proliferation.

Animals↗
PubMed1994

Influence of Losartan, an angiotensin receptor antagonist, on neointimal proliferation in cultured human saphenous vein.

An organ culture of human saphenous vein was used as a model of vein graft intimal hyperplasia and the potential of Losartan, an angiotensin II receptor antagonist, to inhibit neointimal proliferation was investigated. Median (range) neointimal thickness was reduced from 17 (16-19) to 11 (8-18) microns in veins cultured with Losartan (median difference 5 (95 per cent confidence interval 2-8) microns). A similar decrease in the median neointimal proliferation index was seen from 21 (range 14-47) to 15 (range 5-31) per cent (median difference 8 per cent (95 per cent confidence interval 5-11 per cent)). These results demonstrate that angiotensin II receptor antagonists may be of therapeutic value for the modulation of vein graft intimal hyperplasia.

Angiotensin Receptor Antagonists↗
PubMed1994

Differential expression of CD43 (leukosialin, sialophorin) by mononuclear phagocyte populations.

CD43 is a hematopoietic cell antigen whose distribution includes T lymphocytes, plasma cells, neutrophils, and platelets. Although it has been detected on peripheral blood monocytes, its expression by other mononuclear phagocytes has not been well documented. Possible changes in monocyte/macrophage CD43 expression in response to inflammation are also poorly defined. To examine these questions, the expression of CD43 by rat peripheral blood monocytes and both resident and elicited peritoneal macrophages was examined. By flow cytometry with two anti-CD43 monoclonal antibodies, blood monocytes were found to express large amounts of surface CD43, whereas surface CD43 expression by resident peritoneal macrophages was negligible. Peritoneal macrophage populations elicited by intraperitoneal injection of thioglycollate were uniformly positive for surface CD43, although the level of expression was lower than that found on monocytes. By labeling resident macrophages with a fluorescent tracer dye, this phenotypic shift was found to reflect an influx of CD43-positive elicited macrophages coupled with a disappearance of CD43-negative resident cells. Evidence from both flow cytometry and Western blotting studies suggests that the CD43 expressed by elicited peritoneal macrophages is less heavily sialylated than that expressed by blood monocytes. These findings, coupled with recent evidence that CD43 influences cellular adhesion, indicate that differential expression of CD43 may play a role in monocyte/macrophage trafficking.

Animals↗
PubMed1994

Measurement of chloride concentration in microvolume samples of sweat.

Measuring sweat Cl concentration requires multiple steps. Following pilocarpine iontophoresis we compared Cl concentrations of sweat obtained on gauze pads to microvolumes (5 microL) collected into capillary tubes (N = 111). Chloride concentrations obtained by these two methods correlated significantly (r = 0.95; P < 0.001), indicating that Cl concentration can be measured accurately and easily on small volumes.

Chlorine↗
PubMed1994

Air pollution and childhood respiratory health: exposure to sulfate and ozone in 10 Canadian rural communities.

This study was designed to examine differences in the respiratory health status of preadolescent school children, aged 7-11 years, who resided in 10 rural Canadian communities areas of moderate and low exposure to regional sulfate and ozone pollution. Five of the communities were located in central Saskatchewan, a low-exposure region, and five were located in southwestern Ontario, an area with moderately elevated exposures resulting from long-range atmospheric transport of polluted air masses. In this cross-sectional study, the child's respiratory symptoms and illness history were evaluated using a parent-completed questionnaire, administered in September 1985. Respiratory function was assessed once for each child in the schools between October 1985 and March 1986, by the measurement of pulmonary function for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), peak expiratory flow rate (PEFR), mean forced expiratory flow rate during the middle half of the FVC curve (FEF25-75), and maximal expiratory flow at 50% of the expired vital capacity (V50max). The 1986 annual mean of the 1-hr daily maxima of ozone was higher in Ontario (46.3 ppb) than in Saskatchewan (34.1 ppb), with 90th percentile concentrations of 80 ppb in Ontario and 47 ppb in Saskatchewan. Summertime 1-hr daily maxima means were 69.0 ppb in Ontario and 36.1 ppb in Saskatchewan. Annual mean and 90th percentile concentrations of inhalable sulfates were three times higher in Ontario than in Saskatchewan; there were no significant differences in levels of inhalable particles (PM10) or particulate nitrates. Levels of sulfur dioxide (SO2) and nitrogen dioxide (NO2) were low in both regions. After controlling for the effects of age, sex, parental smoking, parental education, and gas cooking, no significant regional differences were observed in rates of chronic cough or phlegm, persistent wheeze, current asthma, bronchitis in the past year, or any chest illness that kept the child at home for 3 or more consecutive days during the previous year. Children living in southwestern Ontario had statistically significant (P < 0.01) mean decrements of 1.7% in FVC and 1.3% in FEV1.0 compared with Saskatchewan children, after adjusting for age, sex, weight, standing height, parental smoking, and gas cooking. There were no statistically significant regional differences in the pulmonary flow parameters (P > 0.05).

Air Pollutants↗
PubMed1994

Respiratory distress secondary to scalds in children.

Respiratory distress secondary to scalds in children is rare. We report 13 children (six girls and seven boys) with a mean age of 19 months who sustained this injury, who were admitted to a major referral hospital during a 5.5-year period. Associated scalds usually to the face were always present and the mean total burn surface area (TBSA) was 14.4 per cent (range 3-30 per cent). Stridor was the most common presenting symptom with a variable time of onset. Bronchoscopy was performed in 11 children and in nine the injury was confined to the supraglottic area. Five children were treated with epinephrine nebulization and the symptoms resolved in 3-4 days, one child had a prophylactic tracheostomy. Seven children required intubation and ventilation. Three children died, two of whom sustained burns to both the upper and lower respiratory tract. Respiratory distress secondary to scalds may not be recognized or the progressive nature of the injury not appreciated. In three-quarters of our patients the injury was confined mainly to above the glottis. Children with inspiratory stridor can be managed with epinephrine nebulization but more marked respiratory distress requires intubation and ventilation. Mortality was due to direct thermal injury to the respiratory tract and secondary bronchopneumonia.

Burns↗
PubMed1994

Human venous endothelium can promote intimal hyperplasia in a paracrine manner.

PURPOSE: Vein graft stenoses resulting from the development of intimal hyperplasia are the major cause of graft failure in the first postoperative year. This study uses an organ culture of human saphenous vein to model vein graft intimal hyperplasia and assess the involvement of the endothelium in its development. METHODS: Organ cultures of saphenous vein were established comprised of intact vein, vein denuded of endothelium, or cocultures of intact plus denuded vein for 14 days in serum-supplemented medium. At the end of the culture period, veins were processed and sections prepared for immunostaining with monoclonal alpha-smooth muscle actin, Millers elastin, QB END.10, and bromodeoxyuridine. RESULTS: After culture, a cellular neointima developed in the intact veins that was significantly thicker than in those denuded of endothelium (24.5 vs 2.5 microns; p = 0.0001). Denuded veins in coculture with intact veins developed a thicker neointima than did denuded veins alone (12 vs 0 microns; p = 0.01) but less than that of intact veins (12 vs 28 microns; p < 0.01). Proliferation indexes followed the same trend (i.e., intimal smooth muscle cell proliferation was greatest in intact and least in denuded veins). CONCLUSION: The endothelium can promote neointimal formation in cultured human saphenous vein through a paracrine action on the vascular smooth muscle cell.

Endothelium, Vascular↗
PubMed1994

The influence of low molecular weight heparin on neointimal proliferation in cultured human saphenous vein.

OBJECTIVES: To investigate the effect of low molecular weight heparin (LMWH) on neointimal proliferation in cultured human saphenous vein, a model of human vein graft intimal hyperplasia. DESIGN: Dose ranging LMWH concentration study. SETTING: Culture Laboratory, Department of Surgery. MATERIALS: Fifteen segments of human long saphenous vein were incubated at 37 degrees C for 14 days in culture medium with 30% foetal calf serum. LMWH was added to one of the paired segments at 1, 10 and 100 micrograms/ml (five veins each dose). 5-bromo-2-deoxyuridine (Brd-U) was used to label proliferating cells. CHIEF OUTCOME MEASURES: Neointimal thickness (micron and proliferation index (% labelled neointimal cells). MAIN RESULTS: Neointimal thickness and proliferation index were both significantly reduced by LMWH at 100 micrograms/ml [control vs. LMWH, reduction in thickness 21 microns vs. 7 microns (median difference 12 microns, 95% conf. int. 6-18), reduction in proliferation index 33% to 6% (median difference 19%, 95% C.I. 4-32)]. CONCLUSIONS: High dose LMWH reduces neointimal proliferation in cultured human saphenous vein. The practical clinical application of these results may require the use of non anticoagulant heparin-like molecules and/or local drug delivery systems.

Cell Division↗