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Biomedical subjects

D Harris

Publications and source records attributed to D Harris.

At least 55 records · Page 3Linked to original sources
PubMed1999

Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities.

The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34(-)13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML.

Apoptosis↗
PubMed1999

Severity of schizophrenia and magnetic resonance imaging abnormalities: a comparison of state and veterans hospital patients.

BACKGROUND: The relationship between illness severity and neuroanatomical abnormalities in schizophrenia remains unclear. The purpose of this study was to test whether the pattern and extent of brain volume abnormalities differed between two patient groups, distinguished by their overall severity and clinical course of schizophrenia. METHODS: Subjects were 56 severely ill, chronically hospitalized schizophrenic men from Napa State Hospital (SH-SZ), 44 moderately ill, acutely hospitalized schizophrenic men from the Palo Alto Veterans Administration Health Care System (VA-SZ), and 52 healthy male control subjects. Temporolimbic, ventricular, and frontoparietal volumes, quantified from 3-mm coronal spin-echo magnetic resonance images and adjusted for cerebral volume and age, were compared using analysis of variance. RESULTS: Compared to control subjects, both SZ groups had smaller (p < .05) temporal lobe and frontoparietal gray matter volumes and larger ventricles and temporal sulci. Whereas SH-SZ had more pronounced cerebrospinal fluid and frontoparietal abnormalities relative to VA-SZ; VA-SZ had greater temporal lobe gray matter deficits. Neither patients group had hippocampal or cerebral volume deficits relative to control subjects. There were no differences between diagnostic subtypes. CONCLUSIONS: The magnitude of volume abnormalities in schizophrenia varies with respect to disease severity and to brain region, but disease severity is not associated with anatomically distinct subgroups.

Adult↗
PubMed1999

Characterization of cannabinoid receptors coupled to vasorelaxation by endothelium-derived hyperpolarizing factor.

We have recently proposed that an endogenous cannabinoid may be an endothelium-derived hyperpolarizing factor (EDHF), and we have now characterized the cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxations to carbachol (ED50=3.26+/-0.57 nmol; the maximum relaxation, Rmax = 87.0+/-2.5%) were opposed by the selective cannabinoid CB1 antagonist, LY320135: at 2 microM ED50 for carbachol was 10.4+/-2.6 nmol and Rmax was 66.9+/-6.2%, at 10 microM ED50 was 15.9+/-4.0 nmol and Rmax was 34.0+/-4.3%. However, these responses were unaffected by another putative CB1 ligand, AM630 (10 microM), or a CB2 selective antagonist, SR 144528 (100 nM-1 microM). None of the antagonists influenced vasorelaxation to either the potassium channel activator levcromakalim or sodium nitroprusside. Coupled to our previous observation that the CB1 receptor antagonist SR141716A opposes EDHF-mediated relaxation, the present observations point to the involvement of a cannabinoid receptor, which may be CB or CB1-like, in EDHF-mediated vasorelaxation.

Animals↗
PubMed1999

The relationship between insulin, IGF-I and weight gain in cystic fibrosis.

OBJECTIVE: In cystic fibrosis, reduced body mass is related to low levels of IGF-I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction. PATIENTS AND DESIGN: We measured serum levels of insulin, IGF-I, IGFBP-I, IGFBP-3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99-17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory. RESULTS: The mean height standard deviation score (SDS (SD)) was -0.54 (0.97) and the body mass index SDS -0.24 (1.09). Both body mass index SDS (r = -0.40, P = 0.0003) and IGF-I SDS (r = - 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF-I and IGFBP-3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP-I were inversely related to those of IGF-I and insulin (r = - 0.43, P = 0. 0004, r = - 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP-I (r = - 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF-I (P = 0. 04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP-I (P = 0.01). CONCLUSIONS: We conclude that progressive insulin deficiency may result in reduced IGF-I levels and IGF-bioactivity and may determine weight gain and statural growth in cystic fibrosis.

Adolescent↗
PubMed1999

The aetiology of acute rupture of flexor tendon repairs in zones 1 and 2 of the fingers during early mobilization.

Five hundred and eight patients with 840 acute complete flexor tendon injuries in 605 fingers in zones 1 and 2 underwent surgery and postoperative mobilization in a controlled or early active motion (active flexion-active extension) regimen over a period of 7.5 years. Sixty-eight patients with 79 finger flexor divisions who did not complete the rehabilitation programme were excluded. Of the 440 patients with 728 complete tendon divisions in 526 fingers included in the study, 23 patients ruptured 28 tendon repair(s) in 23 fingers, an overall rupture rate of 4%. One hundred and twenty-nine fingers with zone 1 injuries had a rupture rate of 5%. Three hundred and ninety-seven fingers with zone 2 injuries had a rupture rate of 4%. This study analyses the 23 patients with flexor tendon rupture(s) to identify causative factors. In approximately half of these patients, tendon rupture followed acts of stupidity. The implications of this are discussed. There was no significant relationship between tendon rupture and the age or sex of the patients, smoking or delay between injury and tendon repair and there was no particular prevalence of zone 2C level injuries among the fingers in which tendon rupture occurred.

Adolescent↗
PubMed1999

The expanded role of acute care nurses: the issue of liability.

For a variety of reasons the activities performed by health care professionals are ever increasing, however the legislative process regulating these specialised workers is not keeping up with the practice realities. While competency statements and credentialling mechanisms are developing, they are not uniformly in place for specialists. Therefore activities completed by these practitioners may be legally controversial. This study documents a variety of tasks completed independently by nurses employed in three acute care hospitals that legally require medical orders and then examines the legal implications of this role extension. Credentialling is one mechanism by which nurses and other health care professionals can ensure they possess the levels of knowledge and skill required to perform the advanced activities required of them and consequently avoid negative legal repercussions.

Australia↗
PubMed1999

A novel percolation method for determining solubilities of pharmaceutical agents in semisolid vehicles.

A novel technique was developed to quantify the solubility of pharmaceutical actives in semisolid formulations. Ointments and emulsions of increasing potencies were sheared to disrupt their internal microcrystalline networks. These sheared materials were held in taut cheesecloth pouches, and the bleed that percolated out was collected and assayed for active potency. The solute concentration in the bleed was proportional to the concentration of the solute in solution in the formulation. Plots of bleed active potency against total formulation potency rose linearly to the point of formulation saturation. Above saturation, bleed potencies remained constant, producing plateaus on the solubility plots. The formulation potency at the onset of plateau quantified the saturation solubility of the active in each formulation. This technique was demonstrated with butylparaben in three ointment bases, and with hydrocortisone in an emulsion formulation. The solubility estimates thus obtained were confirmed experimentally by optical microscopy. This novel technique permits saturation solubilities to be determined for a range of semisolid formulations, with much greater accuracy than was previously possible.

Anti-Inflammatory Agents↗
PubMed1999

Improving a system of care for elderly persons in rural areas.

This article describes a community initiative to improve the care of elders in largely rural areas. An organization development framework guided pilot projects in two communities, with support from a regional geriatric program. Two interdisciplinary teams, representing primary service agencies in the communities, have been trained to serve as local resources in geriatric assessment and intervention. Through the resource teams, the communities are developing a more integrated and coordinated approach to care for the elderly population. The process has yielded valuable insights into the implementation of system change.

Geriatric Assessment↗
PubMed1999

Comparison of the antisecretory effects of omeprazole when administered intravenously, as acid-stable granules and as an oral paste in horses.

The antisecretory activity of omeprazole on gastric acid when administered i.v., intragastrically or per os, was evaluated in 2 female and 3 castrated male horses. Each horse had been prepared with a chronic indwelling gastric cannula. A single i.v. administration of omeprazole (1.5 mg/kg bwt) was effective in abolishing basal and pentagastrin (PG)-stimulated acid secretion. Once daily, nasogastric administration of omeprazole in acid-stable granules for 5 days inhibited acid secretion in a dose-dependent manner: 57% (1.5 mg/kg bwt) and 98% (5.0 mg/kg bwt) reduction of PG-stimulated acid secretion. The degree of inhibition was maintained over a 19 day treatment period with once daily dosing. A prototype oral paste formulation containing either acid-stable omeprazole granules or uncoated omeprazole powder was equipotent when compared to a similar dosage of acid-stable omeprazole granules administered by nasogastric tube. A dose-dependent inhibition was seen with the oral paste formulation containing omeprazole powder: 55% (1.5 mg/kg bwt) and 77% (3.0 mg/kg bwt) reduction of PG-stimulated acid secretion after 5 days. Therefore, a paste formulation of omeprazole powder may offer an effective, easily administered, once daily acid inhibitory treatment for gastric ulcer disease in horses.

Administration, Oral↗
PubMed1999

Linking toluene degradation with specific microbial populations in soil.

Phospholipid fatty acid (PLFA) analysis of a soil microbial community was coupled with (13)C isotope tracer analysis to measure the community's response to addition of 35 microg of [(13)C]toluene ml of soil solution(-1). After 119 h of incubation with toluene, 96% of the incorporated (13)C was detected in only 16 of the total 59 PLFAs (27%) extracted from the soil. Of the total (13)C-enriched PLFAs, 85% were identical to the PLFAs contained in a toluene-metabolizing bacterium isolated from the same soil. In contrast, the majority of the soil PLFAs (91%) became labeled when the same soil was incubated with [(13)C]glucose. Our study showed that coupling (13)C tracer analysis with PLFA analysis is an effective technique for distinguishing a specific microbial population involved in metabolism of a labeled substrate in complex environments such as soil.

Bacteria↗
PubMed1999

Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies.

The role of antibody in protection against human immunodeficiency virus (HIV-1) has been difficult to study in animal models because most primary HIV-1 strains do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed passive-transfer experiments in rhesus macaques to study the role of anti-envelope antibodies in protection. Based on prior in vitro data showing neutralization synergy by antibody combinations, we evaluated HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and the triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were completely protected; the remaining three animals became SHIV infected but displayed reduced plasma viremia and near normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only transient evidence of infection; the other two had marked reductions in viral load. All monkeys that received HIVIG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia. However, compared to controls, monkeys that received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a more benign clinical course. These data indicate a general correlation between in vitro neutralization and protection and suggest that a vaccine that elicits neutralizing antibody should have a protective effect against HIV-1 infection or disease.

AIDS Vaccines↗
PubMed1999

Drinking and flying: a structural model.

BACKGROUND: Under a recent revision of the European Joint Aviation Authorities operations regulations it has been prohibited to act as a crew member of an aircraft with a BAC of greater than 0.02%. METHODS: This survey of UK Civil Aviation Authority pilots suggests that over 50% of respondents may have flown an aircraft with a BAC of greater than this prescribed amount. RESULTS: Professional pilots were found to be heavier drinkers than private pilots and were also more likely to infringe the 0.02% BAC rule. CONCLUSION: Analysis of the data using path analysis suggests that professional pilots may be more prone to offending as a result of training in a "drinking culture" and as a response to commercial pressures in the industry.

Adult↗
PubMed1999

Diabetes and obesity in the Louisiana Coushatta Indians.

OBJECTIVE: In order to assist their community in planning intervention and prevention programs, prevalence rates for diabetes and obesity were examined among the Louisiana Coushatta. RESEARCH DESIGN AND METHODS: Coushatta individuals participated in a health survey (questionnaires and physical examinations). Those without known diabetes underwent oral glucose tolerance testing and were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). Those with known DM had the diagnosis confirmed by history and/or elevated hemoglobin A1c. Waist-to-hip ratio (WHR), body mass index (BMI), and percent body fat (%BF) were determined as measures of central adiposity and obesity. Prevalence rates of diabetes and obesity among those examined were calculated. The prevalence of those with more than one anthropometric index positive for obesity was also determined. RESULTS: The prevalence of DM was 30% and IGT was 17% among the first 151 Coushatta participants. For males, the prevalence of obesity was 62%, 57%, and 52%, and for females, 59%, 54%, 45%, as determined by the BMI, %BF, and WHR, respectively. Obesity was more prevalent among those with glucose intolerance (IGT + DM) than those with NGT, and those who were obese had the highest prevalence of glucose intolerance. A greater percentage of those with glucose intolerance had more than one positive obesity measure as compared to those with NGT, and those with more than one index consistent with obesity had a greater prevalence of IGT + DM. CONCLUSIONS: Prevalence rates of DM and obesity are high among the Louisiana Coushatta, and obesity is associated with glucose intolerance. Clustering of the three obesity measures occurs in a high percentage of individuals. Data from the current survey are providing information that is being used by the Coushatta community for health planning and development of intervention and prevention programs.

Adolescent↗
PubMed1999

Application of ChromaGen haploscopic lenses to patients with dyslexia: a double-masked, placebo-controlled trial.

BACKGROUND: Many patients with dyslexia report distortion to text when they are reading. After a successful pilot trial of an improvement in reading rate using ChromaGen haploscopic filters in comparison with the Intuitive Colorimeter, a full-scale, randomized, cross-over, double-masked, placebo-based trial was undertaken. METHOD: The Wilkins rate of reading test was used to produce a baseline score, against which scores with ChromaGen lenses, placebo lenses, and a control were compared. Exclusion criteria included no formal dyslexia diagnosis, contraindications to contact lens wear, and uncorrected visual causes for reading difficulty. RESULTS: Forty-seven individuals successfully completed the trial, of which 41 reported distortion to the text (e.g., words appeared to move, were blurred, or patterns or spaces seemed to form in the text) when the patients were reading, and nine were color deficient. A comparison trial of ChromaGen lenses with placebo lenses demonstrated a significant improvement in the reading rate with ChromaGen lenses in individuals who reported distortion to text (p = 0.05) and a highly significant improvement in non-color-deficient individuals who reported distortion (p = 0.006). T-tests of the repeated measures showed that ChromaGen lenses produced a highly significant improvement in the rate of reading--over and above the placebo--in non-color-deficient individuals who reported distortion (p < 0.0001). CONCLUSION: The significant increase in the reading rate amongst those who reported distortion suggests that by decreasing the distortion to text, a substantial proportion of dyslexic patients--in combination with their normal reading programs--would benefit from this aid.

Adolescent↗
PubMed1999

Caspase 2 and caspase 3 as predictors of complete remission and survival in adults with acute lymphoblastic leukemia.

Dysregulation of apoptosis is an important mechanism in leukemogenesis. Caspases are cysteine proteases that play a major role in the activation of apoptotic pathways and chemotherapy-induced cell death. High levels of inactive, uncleaved caspase 2 and caspase 3 have recently been associated with poor survival in patients with acute myelogenous leukemia. We hypothesized a similarly significant role for caspase 2 and caspase 3 in patients with acute lymphoblastic leukemia. We determined levels of uncleaved caspase 2 and caspase 3 by quantitative Western blot analysis in peripheral blood samples of 45 adults with newly diagnosed ALL. We evaluated patient prognostic variables and caspase levels using multivariate logistic and Cox regression models to determine their impact on complete remission rate and overall survival probability. Levels of caspase 2 and, to a lesser degree, caspase 3 were highly associated with cytogenetic abnormalities, with lower levels in the diploid group (P = 0.016 and P = 0.10, respectively). No association between either caspase level and the percentage of bone marrow blasts was found. A high level of caspase 3 (>0.37 as determined graphically) was significantly associated with achieving complete remission (CR; P = 0.006). A multivariate logistic regression analysis including age, WBC count, percentage of peripheral and marrow blasts, hemoglobin, albumin, lactate dehydrogenase, bilirubin, and creatinine determined that a high level of caspase 3 was the most significant predictor of CR (P = 0.025, adjusted), with albumin the only other significant variable (P = 0.031). Caspase 2 levels were not associated with probability of CR. In a multivariate Cox model for survival, however, levels of caspase 2 above 0.37 were associated with a lower survival probability than were levels below that threshold (P = 0.064). High levels of caspase 3 may have a significant effect on achieving CR. Because of the limited power (n = 45) of our study, the significance of caspase 2 and caspase 3 on overall survival remains to be validated by further investigations.

Adolescent↗