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Biomedical subjects

J L Anderson

Publications and source records attributed to J L Anderson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells.

Enhanced proliferation of airway smooth muscle is thought to contribute to the pathogenesis of asthma and other obstructive airway diseases. Lysophosphatidic acid (LPA) is a simple bioactive lipid mediator that stimulates mitogenesis in fibroblasts and some other cell types. The effects of LPA on mitogenesis of cultured human airway smooth muscle cells were determined by measuring [3H]thymidine incorporation into cellular DNA. LPA induced a concentration-dependent stimulation of [3H]thymidine incorporation of a similar magnitude to that induced by serum, with the effects of 50 microM LPA being similar to those of 5% serum. Stimulation by LPA and by serum was almost completely eliminated in cells exposed to pertussis toxin, indicating involvement of a pertussis toxin-sensitive G protein in mitogenic signaling by these agents. Epidermal growth factor (EGF) induced stimulation of a similar magnitude as that with LPA, but the stimulation by EGF was insensitive to pertussis toxin. LPA and EGF, when added together, exhibited a markedly synergistic stimulation of [3H]thymidine incorporation that was typically 10-fold greater than the stimulation with either agent alone. LPA and EGF also stimulated mitogenesis assessed by cell growth, and again LPA and EGF together exhibited synergism. These results suggest the possibility that stimulation of airway smooth muscle cell proliferation by LPA, either alone or by enhancing effects of other growth factors, could play a role in normal airway remodeling or in the pathological proliferation of smooth muscle in various airway diseases.

Cell Division↗
PubMed1997

Validity and reliability of rapidly alternating movement tests.

Two studies investigated the interrater reliability and concurrent validity of tests of rapidly alternating movement. Study I examined the interrater reliability of three different tests, "finger tapping" to the adjacent thumb, "table tapping," and "hand to thigh" alternating movements. Using normal participants the results indicated poor interrater agreement for the "hand to thigh" test and modest relationship for both types of finger tapping. However, for each test the number of recorded repetitions differed significantly between raters. Study 2 examined the concurrent validity of two mechanical measures of finger tapping. The scores of 36 normal participants was compared using a mechanical digital counter and a calculator. Results indicated that the use of the calculator as a counter was highly related to the results with a mechanical digital counter. Conclusions suggested the use of a mechanical apparatus is more reliable than human observations. In addition, the use of an inexpensive apparatus will produce results similar to the manual finger tapping apparatus commonly used in neuropsychological batteries.

Adult↗
PubMed1997

Association of genetic variations in apolipoprotein B with hypercholesterolemia, coronary artery disease, and receptor binding of low density lipoproteins.

To search for unique mutations in the apolipoprotein B (apoB) gene that disrupt the binding of LDL to its receptor and cause hypercholesterolemia, we examined more than 800 patients with high LDL cholesterol levels and/or coronary artery disease (CAD). Analysis of patient DNA by single-strand conformation polymorphism and allele-specific oligonucleotide hybridization of the sequence surrounding the putative receptor- binding domain of apoB (amino acid positions 2965 to 3534) revealed seven variations. LDL from heterozygotes with either Arg 3500 Gln or Arg 3531 Cys bound defectively with the LDL receptor in competitive binding assays. The Arg 3500 Gln substitution was statistically more prevalent in patients with hypercholesterolemia (P = 0.0003). Total cholesterol and LDL-cholesterol were significantly higher (P< 0.0004) in 34 apoB 3500 Gln carriers than in the controls. The allele encoding the Arg 3531 Cys substitution was more prevalent (0.8%) in the CAD group (P = 0.05) than in the controls. A Ser 3252 Gly variant was statistically more prevalent in the hypercholesterolemic group (P = 0.03), but LDL with this mutation had normal LDL receptor-binding activity. The other four variants identified (Leu 3350 Leu, Gln 3405 Glu, Val 3396 Met, and Ser 3455 Arg) were not associated with defective LDL-receptor binding, hypercholesterolemia, or CAD, nor were the apoB mutations associated with elevated lipid levels in family members. The surprising result that only two mutations of apoB in the receptor-binding domain (Arg 3500 Gln and Arg 3531 Cys) were associated with defective LDL binding, hypercholesterolemia, or CAD is in stark contrast with familial hypercholesterolemia, where nearly 150 mutations of the LDL receptor have been described that disrupt its function. This study strongly suggests that a limited number of mutations of apoB markedly influence LDL binding to its receptor.

Adult↗
PubMed1997

Relationship of two apolipoprotein B polymorphisms with serum lipoprotein and lipid levels in African blacks.

Two DNA polymorphisms, insertion/deletion (ins/del) and XbaI, of the apolipoprotein B (APOB) gene and their relationships with serum lipoprotein and lipid levels were examined in two Nigerian populations from Benin (n = 828) and Sokoto (n = 394). Allele frequencies for both polymorphisms were comparable between the two populations, and genotype frequencies conformed to Hardy-Weinberg equilibrium expectations. Because lipid profiles are affected by many known sex differences, males and females were analyzed separately. Analysis of variance was performed to test equality of means of quantitative traits across genotypes; the dependent variables were first adjusted by stepwise linear regression for environmental covariates in both populations. Plasma apoB and HDL2 cholesterol levels varied significantly between ins/del genotypes in Benin males (p = 0.05) and Sokoto males (p = 0.02), respectively. No significant variation between XbaI genotypes was observed for any lipid trait in either population. Combining the ins/del and XbaI polymorphisms to form haplotypes revealed significant linkage disequilibrium in both the Benin (p < 0.0001) and Sokoto (p < 0.001) populations. Analysis of the two-site haplotype showed a significant effect on serum lipoprotein (a) levels in Benin females (p < 0.04) and on HDL2 cholesterol among Sokoto males (p = 0.01). The haplotype explained 4% of the adjusted phenotypic variation in lipoprotein (a) levels in Benin females and 8.5% of the adjusted phenotypic variation in HDL2 cholesterol levels in Sokoto males. These data indicate that the ins/del and XbaI polymorphisms in the APOB gene affect interindividual variation in serum lipoprotein and lipid levels in African populations.

Analysis of Variance↗
PubMed1997

Inducing practice guidelines from a hospital database.

Improving health care quality requires the elimination of unnecessary variation in the care process. Decision support applications already exist that can foster adherence to standards. The challenge resides in developing standards consistent with good medical practice. In this paper we present our efforts in determining where sufficient clinical data are captured electronically to automatically define a care process, and what analyses can be done to identify additional data that would allow a care process to be defined. Data routinely collected by a hospital information system have been examined. The analysis tools utilized include logistic regression, a neural network, a Bayesian network, and a rule induction program.

Bayes Theorem↗
PubMed1996

Cytokines and rejection of mouse cardiac allografts.

Graft survival is prolonged by pretransplant transfusion of the graft recipient. It has been postulated that graft rejection is associated with Th1-like cytokines. We tested whether transfusion shifts cytokine production from a Th1-type (gamma-IFN production) to a Th2-type (IL-4 production). Transfusion prolonged cardiac allograft (C3H/HeN donor to a C57BL/6 recipient) survival (10.4+/-0.5 versus 7.2+/-0.2 days for controls, P<0.0001). Splenocyte cultures from nontransfused recipients produced supernatant IFN-gamma concentrations of 13.4+/-1.4 ng/ml upon anti-CD3 stimulation; the same cells produced 32.3+/-3.5 pg/ml IL-4 stimulated with Con A. Spleen cells from transfused animals did not produce gamma-IFN with or without stimulation; (P<0.0001) and produced 21.5+/-3.2 pg/ml IL-4 without stimulation (P<0.0001 compared with controls). C57BL/6 CD8+ lymphocytes isolated from rejected C3H grafts were adoptively transferred (6.7+/-1x10(6)/animal) to pretransfused, C57BL/6 recipients of a C3H graft. Graft survival for these recipients was 7.8+/-0.3 days compared with 10.4+/-0.5 days for recipients pretreated with transfusion only (P<0.005). Transcripts of the gamma-IFN gene were present in unmodified grafts but not in the grafts from transfused recipients given the CD8 cells. In conclusion, transfusion downregulated gamma-IFN production and up-regulated IL-4 production and slowed (but did not abrogate) rejection; CD8 graft-infiltrating cells given adoptively restored normal rejection but not IFN-gamma. Further studies are needed to elucidate the role of cytokines in cardiac allograft rejection.

Adoptive Transfer↗
PubMed1996

Explaining discrepant mortality results between primary percutaneous transluminal coronary angioplasty and thrombolysis for acute myocardial infarction.

Differing relative outcomes in randomized versus registry studies comparing primary angioplasty with thrombolytic therapy for acute myocardial infarction suggest a clinical paradox. A predictive model based on differences in 5 treatment-related factors, including time to therapy, patency success, and angioplasty experience, suggests that relative outcomes may indeed vary, depending on the clinical setting in which therapy is given.

Algorithms↗
PubMed1996

Safety and tolerability of long-term propafenone therapy for supraventricular tachyarrhythmias. The Propafenone Multicenter Study Group.

An important issue regarding the long-term use of antiarrhythmic drugs concerns the safety of these agents, particularly with regard to cardiac toxicity. Propafenone is an effective drug for preventing supraventricular tachyarrhythmia, but the incidence of side effects during longterm therapy in patients with such arrhythmias has not been adequately reported. A total of 480 patients received oral propafenone as therapy for symptomatic atrial fibrillation, atrial flutter, or supraventricular tachycardia. During the follow-up (mean 14.4 months), 290 patients (60%) discontinued propafenone therapy, but in only 70 patients (15%) was the reason for discontinuation an adverse drug reaction. Overall, 284 patients (59%) experienced at least 1 adverse reaction, and the incidence was related to dose and age >65 years. The overall incidence of side effects was not related to structural heart disease; however, cardiovascular toxicity including arrhythmia aggravation, congestive heart failure, and serious conduction disturbances occurred more often in those with heart disease (20% vs 13%). Sixteen patients died during drug therapy, but in only 1 case was the drug considered contributory. For patients with a supraventricular arrhythmia, propafenone was well tolerated and was infrequently discontinued because of side effects. The incidence of serious cardiac toxicity when propafenone was used to treat supraventricular arrhythmia was low, and these side effects were more frequent in patients with structural heart disease.

Administration, Oral↗
PubMed1996

Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction.

Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction (AMI). The Thrombolysis in Myocardial Infarction (TIMI) study grading scale for coronary perfusion has gained wide acceptance, but the significance of individual grades on clinical outcome has not been adequately tested. We hypothesized that optimal outcomes would be achieved only with early (and maintained) TIMI grade 3 (complete) perfusion compared with TIMI grade 2 (partial perfusion, previously classified as a reperfusion success) or grades 0 or 1 (occluded arteries). Five recent, angiographically controlled, prospectively performed studies of thrombolysis in AMI were identified, representing 3,969 patients. Odds ratios for mortality by early perfusion grades were calculated using the Mantel-Haenszel test and combined in a weighted fashion. Results for selected clinical and laboratory outcomes by patency grade were also assessed. Overall, mortality averaged 8.8% for TIMI grade 0/1, 7.0% for grade 2, and 3.7% for grade 3 perfusion. The odds ratio (OR) for early mortality was substantially reduced for grade 3 versus <3 perfusion (OR = 0.45, confidence interval [CI] 0.34 to 0.61, p <0.0001). In pairwise comparisons, grade 3 was clearly superior to grade 2 (OR = 0.54, CI) 0.37 to 0.78, p = 0.001) as well as grades 0/1 (OR = 0.41, CI 0.30 to 0.56, p <0.0001). Acute and convalescent ejection fraction, regional wall motion, time to enzyme peaks (creatine kinase [CK], creatine kinase myocardial bond [CK-MB]), peak enzyme levels [CK, lactate dehydrogenase [LDH], LDH-1), and risk of heart failure were each significantly less in patients achieving grade 3 than grade 2 (or lower grades) perfusion. Results were observed despite the frequent use of interventions after angiography. This meta-analysis demonstrates that early and complete (grade 3) flow is associated with superior survival and clinical outcome; grade 2 perfusion results in an inferior outcome, closer to that of an occluded than an open artery. The goal of reperfusion strategies should be early and maintained TIMI grade 3 perfusion.

Coronary Circulation↗
PubMed1996

Regulation of hamster alpha 1B-adrenoceptors expressed in Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells were stably transfected to express the hamster alpha 1B-adrenoeceptor, and the function and agonist-induced regulation of the binding properties of these receptors were characterized. The cells expressed approximately 230,000 receptors per cell, with a KD for [3H]prazosin of 140 pM. In assays of competition by epinephrine for [3H]prazosin binding to receptors on intact cells, 88% of the receptors were in a low affinity form. The protein kinase C activator phorbol 12-myristate, 13-acetate (PMA) did not further increase the fraction in the low affinity form, but the protein kinase C inhibitor staurosporine reduced the low affinity fraction to 51%. In sucrose density gradient centrifugation assays of receptor internalization, the percentage of receptors in the light vesicle fraction was 25% for control cells, 53% for epinephrine-pretreated cells, 44% for PMA-pretreated cells, and 53% for cells pretreated with epinephrine plus PMA. Staurosporine completely blocked PMA-induced internalization, but only partially inhibited epinephrine-induced internalization. These results suggest a relationship between low affinity binding and internalization for alpha 1B-adrenoceptors and the involvement of protein kinase C in both processes. Longer-term (24 h) exposure of cells to epinephrine induced an unexpected up-regulation of receptor density of approximately 2-fold that was accompanied by an increase in maximal agonist-stimulated phosphoinositide turnover. These studies document several regulatory differences between alpha 1B-adrenoceptors expressed in transfected CHO cells and those natively expressed in DDT1 MF-2 hamster smooth muscle cells, and they provide additional information on the molecular mechanisms involved in agonist-induced regulation of alpha 1B-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1996

Development of an in vivo model of human multiple myeloma bone disease.

Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma, SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones were obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total 45Ca released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte-macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cell plated). Bone-resorbing human and murine cytokines such as interleukin-6 (IL-6), IL-1 alpha or beta, TGF-alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total 45Ca released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total 45Ca released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma.

Animals↗
PubMed1996

Safety assessment of a nematode-resistant tomato by a simple, short-term rat feeding study.

A simple, 11-week, weanling rat feeding period was used to determine general safety of a nematode-resistant tomato cultivar. Comparison of growth, mean blood hemoglobin, hematocrit, red blood cell count, and total white blood cell count of Fisher rats fed a complete diet containing 40% "VFN 8" tomato (nematode-resistant) cultivar to two other groups of rats, fed either a "New Yorker" tomato (nematode-susceptible) or a control diet, showed normal and similar results. Although the expressed product of the Mi gene necessary for nematode resistance is unknown, this short, comparative study of a whole plant food shows no unexpected toxicants influencing animal growth and hematology. However, human exposure of this resistant tomato would be needed to definitely determine consumer safety regarding allergenicity and hypersensitivity.

Animal Feed↗
PubMed1996

Hyperadrenergic state following acute withdrawal from clonidine used at supratherapeutic doses.

Abrupt cessation of clonidine treatment precipitates a physiological withdrawal syndrome, thought to be due to a hyperactive state of central autonomic and cognitive adrenergic neuronal systems dependent on presynaptic alpha 2-adrenoceptors and/or imidazoline receptors. We hereby describe a 36-year-old male with history of end-stage renal disease, hypertension and medication non-compliance, who presented with severe hypertension and remarkable agitation. His daily clonidine intake was estimated to be 10 mg. The patient had abruptly discontinued his clonidine five days prior to admission. The following indices of adrenergic activity were measured in plasma (normal control values in parentheses): noradrenaline (NA) 8.59 nmol/l (1.32-4.56 nmol/l), adrenaline (Adr) 1.86 nmol/l (0.83-4.20) nmol/l), total 3-methoxy-4-hydroxyphenylglycol (MHPG) 152.8 nmol/l (45.1-111.5 nmol/l), and free MHPG 33.0 nmol/l (12.2-31.4 nmol/l). Plasma clonidine level was 3.53 ng/ml (15.9 nmol/l) with the usual therapeutic level being < 2.0 ng/ml (8.9 nmol/l). Initially, the patient received sedatives and was started on clonidine for the first 24 hours only, after which time period prazosin was started, with good response of his blood pressure and reversal of his mental status changes. At that point, the plasma values of indices of adrenergic activity had decreased compared with their corresponding initial values by the following percentages: NA 60.6%, Adr 22.6%, total MHPG 42.2% and free MHPG 11.5%. Plasma clonidine level had decreased now by 43.6% to an absolute value of 1.99 ng/ml (8.85 nmol/l). We emphasize that physicians should be aware of clonidine's abuse potential and caution should be taken, as well as the appropriate route chosen, when prescribing clonidine in patients who show features of poor compliance to medications and especially in patients with psychoses, suicide potential or personality disorders.

Adrenergic alpha-Agonists↗