Search PubMed⌕ Search

Biomedical subjects

N Tumer

Publications and source records attributed to N Tumer.

At least 19 recordsLinked to original sources
PubMed2001

Control of enzymatic browning in potato (Solanum tuberosum L.) by sense and antisense RNA from tomato polyphenol oxidase.

Polyphenol oxidase (PPO) activity of Russet Burbank potato was inhibited by sense and antisense PPO RNAs expressed from a tomato PPO cDNA under the control of the 35S promoter from the cauliflower mosaic virus. Transgenic Russet Burbank potato plants from 37 different lines were grown in the field. PPO activity and the level of enzymatic browning were measured in the tubers harvested from the field. Of the tubers from 28 transgenic lines that were sampled, tubers from 5 lines exhibited reduced browning. The level of PPO activity correlated with the reduction in enzymatic browning in these lines. These results indicate that expression of tomato PPO RNA in sense or antisense orientation inhibits PPO activity and enzymatic browning in the major commercial potato cultivar. Expression of tomato PPO RNA in sense orientation led to the greatest decrease in PPO activity and enzymatic browning, possibly due to cosuppression. These results suggest that expression of closely related heterologous genes can be used to prevent enzymatic browning in a wide variety of food crops without the application of various food additives.

Biotechnology↗
PubMed2001

Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins.

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups (n = 12/group): 1) control, 2) exercise (60 min/day) at 4 degrees C (E-Cold), and 3) exercise (60 min/day) at 25 degrees C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher (P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/dt), and pressure relaxation over time (-dP/dt) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher (P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts (P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.

Animals↗
PubMed1999

The effects of exercise duration on adrenal HSP72/73 induction in rats.

This study investigated the effects of varying durations of exercise training on heat shock proteins 72 and 73 (HSP72/73) induction in the rat adrenal gland. Female Sprague-Dawley rats (120 days old) were assigned to either a sedentary control group (C) or one of the three endurance exercise training groups. Trained animals ran on a treadmill at approximately 75% VO2max for 10 weeks (4-5 days week-1) at one of the three different exercise durations (30 min day-1=T30, 60 min day-1=T60, or 90 min day-1=T90). All durations of exercise training resulted in an increase in the HSP72 levels (P < 0.0001). The magnitude of the training-induced elevation in the HSP72 levels in the adrenal gland increased as a function of the training duration ( approximately 60-fold increase in T90; approximately 40-fold increase in T60; and approximately 15-fold increase in T30). Longer exercise durations (>60 min day-1), also resulted in small but significant increase in HSP73 level ( approximately 1.2-fold increase in both T60 and T90; P < 0.05). These results demonstrate that the physiological stress created by chronic treadmill running can induce both HSP72 and HSP73 in rat adrenal gland. Increased levels of adrenal HSP72/73 expression during rigorous exercise, may be one of the adaptive mechanisms of the adrenals to cope with an increased dose of stress.

Adaptation, Physiological↗
PubMed1997

Plant resistance to fungal infection induced by nontoxic pokeweed antiviral protein mutants.

Pokeweed antiviral protein (PAP), a 29-kD protein isolated from Phytolacca americana inhibits translation by catalytically removing a specific adenine residue from the large rRNA of the 60S subunit of eukaryotic ribosomes. Transgenic plants expressing PAP are resistant to a broad spectrum of plant viruses. Nontoxic PAP mutants have been isolated by random mutagenesis and selection in yeast. One of these mutants, PAP-X, had a point mutation at the active-site (E176V) that abolished enzymatic activity, and another mutant, delta C25PAP, had a nonsense mutation near the C-terminus (W237stop) that deleted 25 C-terminal amino acids. Unlike the wild-type PAP, expression of neither mutant was toxic to transgenic plants. We show that both class I (basic) and class II (acidic) isoforms of pathogenesis-related (PR) proteins are overexpressed in transgenic plants expressing PAP and the nontoxic PAP mutants. Although PR-proteins are constitutively expressed, no increase in salicylic acid levels was detected. Homozygous progeny of transgenic plants expressing either PAP or the nontoxic PAP mutants displayed resistance to the fungal pathogen Rhizoctonia solani. These results show that expression of PAP or the nontoxic PAP mutants activates multiple plant defense pathways independently of salicylic acid and confers resistance to fungal infection. The C-terminal 25 amino acids of PAP, which are required for toxicity in vivo, are not critical for resistance to viral or fungal infection, indicating that toxicity of PAP can be separated from pathogen resistance.

Antiviral Agents↗
PubMed1997

Pharmacokinetic features, immunogenicity, and toxicity of B43(anti-CD19)-pokeweed antiviral protein immunotoxin in cynomolgus monkeys.

We studied the pharmacokinetic features, immunogenicity, and toxicity of B43-pokeweed antiviral protein (PAP) immunotoxin in 13 cynomolgus monkeys. The disposition of B43-PAP in two monkeys, when administered as a single i.v. bolus dose, was characterized by a slow clearance (1-2 ml/h/kg) with a very discrete peripheral distribution. B43-PAP was retained and distributed largely in the blood as the sole compartment with no significant equilibration with the extravascular compartment. The circulating B43-PAP immunotoxin detected in monkey plasma samples by ELISA and protein immunoblotting was both immunoreactive with, and active against, human leukemic cells in vitro. In systemic immunogenicity and toxicity studies, which involved 11 cynomolgus monkeys, each monkey received a total of seven i.v. doses of B43-PAP at a specific dose level of the dose escalation schedule. B43-PAP-treated monkeys mounted a dose-dependent humoral immune response against both the mouse IgG and PAP moieties of the immunotoxin. When administered i.v. either on an every-day or every-other-day schedule, B43-PAP was very well tolerated, with no significant clinical or laboratory signs of toxicity at total dose levels ranging from 0.007 to 0.7 mg/kg. A transient episode of a mild capillary leak with a grade 2 hypoalbuminemia and 2+ proteinuria was observed at total dose levels equal to or higher than 0.35 mg/kg. At total dose levels of 3.5 and 7.0 mg/kg, B43-PAP caused dose-limiting renal toxicity due to severe renal tubular necrosis. The present study completes the preclinical evaluation of B43-PAP and provides the basis for its clinical evaluation in children with therapy-refractory B-lineage acute lymphoblastic leukemia.

Animals↗
PubMed1997

In vivo toxicity, pharmacokinetics, and antileukemic activity of TXU (anti-CD7)-pokeweed antiviral protein immunotoxin.

We evaluated the TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunotoxin in both murine and nonhuman primate models. TXU-PAP caused dose-limiting cardiac toxicity in BALB/c mice. In a SCID mouse model of invariably fatal human T-lineage acute lymphoblastic leukemia (ALL), TXU-PAP therapy resulted in a marked improvement of leukemia-free survival without any side effects. Whereas 100% of control mice treated with PBS, unconjugated TXU antibody, or B43-PAP (an immunotoxin that does not react with T-lineage ALL cells) died of disseminated human leukemia within 80 days (median survival, 37 days), 80 +/- 13% of SCID mice treated with 15 microgram of TXU-PAP (median survival, >120 days) and 100% of mice treated with 30 microgram of TXU-PAP (median survival, > 120 days) remained alive and free of leukemia for >120 days. In cynomolgus monkeys, TXU-PAP showed favorable pharmacokinetics with an elimination half-life of 8.1-8.7 h. The monkeys treated with TXU-PAP at dose levels of 0.05 mg/kg/day x 5 days and 0.10 mg/kg/day x 5 days tolerated the therapy very well, without any significant clinical compromise or side effects, and at necropsy, no gross or microscopic lesions were found. This study provides a basis for further evaluation of TXU-PAP as an investigational biotherapeutic agent in the treatment of T-lineage ALL.

Animals↗
PubMed1995

In vitro and in vivo antileukemic activity of B43-pokeweed antiviral protein against radiation-resistant human B-cell precursor leukemia cells.

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and represents one of the most radiation-resistant forms of human malignancy. In this study, we examined the antileukemic efficacy of the B43 (anti-CD19)-pokeweed antiviral protein (B43-PAP) immunotoxin against radiation-resistant BCP leukemia cells. B43-PAP caused apoptosis of radiation-resistant primary BCP leukemia cells, killed greater than 99% of radiation-resistant primary leukemic progenitor cells from BCP leukemia patients, and conferred extended survival to severe combined immunodeficiency (SCID) mice xenografted with radiation-resistant human BCP leukemia. Furthermore, the combination of B43-PAP and total body irradiation (TBI) was more effective than TBI alone in two SCID mouse bone marrow transplantation models of radiation-resistant human BCP leukemia. Thus, B43-PAP may prove useful in the treatment of radiation-resistant BCP leukemia.

Animals↗
PubMed1995

Myosin heavy chain composition in young and old rat skeletal muscle: effects of endurance exercise.

The objective of this study was to determine the effects of age and exercise on the myosin heavy chain (MHC) composition of skeletal muscle. Young (3 mo) and old (22 mo) female specific pathogen-free barrier-reared Fischer 344 rats were randomly assigned to young untrained or young trained and old untrained or old trained groups, respectively. Young trained and old trained animals performed endurance exercise training on a motorized treadmill for 8 wk. Succinate dehydrogenase activity and MHC isoforms were measured in the plantaris (Plan), lateral and medial gastrocnemius (Gast), and soleus (Sol) muscles. In sedentary animals, aging resulted in a decrease (P < 0.05) in type IIb MHC and an increase (P < 0.05) in type IIa MHC in both the Gast and Plan muscles. Also, aging resulted in a small but significant increase (approximately 4%; P < 0.05) in type I MHC in the Sol. Exercise training resulted in significant (P < 0.05) increases in Gast, Plan, and Sol succinate dehydrogenase activity in both young and old animals. Furthermore, exercise training resulted in a decrease (P < 0.05) in the percentage of type IIb MHC and an increase (P < 0.05) in the percentage of type IIa MHC in the Plan in both young and old animals. These data suggest that there is an age-related shift in locomotor muscle MHC isoforms from a faster to a slower isoform.

Age Factors↗
PubMed1993

The effect of phenobarbital on autonomic function and epileptogenic activity induced by the hippocampal injection of penicillin in cats.

This study addressed whether penicillin-induced epileptiform discharges in the right hippocampus produced associated autonomic dysfunction. The study also examined the effect of phenobarbital on the heart rate and blood pressure changes that were induced by the epileptiform discharges. The delay in onset of epileptiform activity at the site of injection ranged from 1 second to 16 minutes, and consisted of interictal discharges or ictal discharges. With the onset of epileptiform activity, blood pressure and heart rate increased significantly from control (P < .05). Electrocardiogram alterations included: P-R interval changes; increased P-wave amplitude; QRS complex changes; T-wave inversion; and ST elevation. Phenobarbital 20 mg/kg intravenously suppressed the epileptogenic activity and depressed the blood pressure and heart rate below control (P < .05). In an additional series of experiments, penicillin G injected into the right hippocampus in five cats produced epileptiform activity and increased the blood pressure and the heart rate significantly from the control (P < .05). Phenobarbital (20 mg/kg, intravenously, and 40 mg/kg, intravenously) also prevented the penicillin-induced epileptiform activity. Phenobarbital (40 mg/kg, intravenously) reversed the effect of penicillin on the blood pressure and heart rate, to levels significantly below that of control (P < .05). Phenobarbital diminished both epileptiform activity and autonomic dysfunction. The autonomic dysfunction related to epileptiform activity induced by focal hippocampal administration of penicillin was similar to that induced by the intravenous administration of pentylenetetrazol.

Animals↗
PubMed1992

Gender differences in the effect of age on adrenergic neurotransmission in the heart.

In male rats, there is an age-associated decline in the capacity of cardiac sympathetic nerves to release norepinephrine. To investigate whether this phenomenon also occurs in female rats, we examined adrenergic neurochemical transmission in the hearts of female and male Fischer 344 rats. Rats aged 6, 12, and 24 months were employed. Hearts with the right cardiac sympathetic nerve intact were isolated and perfused with Krebs-Ringer solution. Stimulations were performed following the administration of cocaine or metanephrine separately and in combination or following the combination of cocaine, metanephrine, and yohimbine. Cocaine (1 microM) was used to block uptake 1, metanephrine (1 x 10(-5) M) to block uptake 2, and yohimbine (3 microM) to block alpha 2 receptor presynaptically. The nerve was stimulated with frequencies of 2, 6, and 12 Hz, and norepinephrine amount in the effluent was determined by high performance liquid chromatography/electrochemical detection methods. Neither norepinephrine release nor the effects of yohimbine, cocaine, or metanephrine were found to be affected in older female rats (24 month). This suggests that age-related changes in adrenergic neurochemical transmission in the heart of female rats differ from those seen in older male rats.

Aging↗
PubMed1991

Effect of age on presynaptic beta2 receptor mediated responses in the rat heart.

Presynaptic alpha2 adrenergic receptor inhibition of norepinephrine (NE) release is diminished in older animals [1]. To determine whether presynaptic beta2 adrenergic receptor facilitation of NE release is also affected by age, the effect of propranolol on neurally-induced NE release was examined in perfused heart preparations isolated from 6- and 24-month-old rats. The heart was isolated with the right cardiac sympathetic nerve and then was stimulated electrically in the absence and presence of propranolol (10(-8)-10(-6) M). NE content in the effluent was measured by an HPLC/EC methodology. The data indicate that there is a greater suppression of NE release by propranolol in preparation isolated from younger animals. For example, in nerve-heart preparations of 6-month-old animals stimulated at 12 Hz, propranolol (10(-6) M) reduced the amount of NE released by 34% whereas in preparations from 24-month-old animals at 12 Hz there was no significant change in the NE overflow. Like the alpha2 receptor mechanism, autoregulation of NE release by presynaptic beta2 receptors is diminished in older animals. Lack of presynaptic autoregulation may explain in part, the reduced capacity of adrenergic influences to control and regulate cardiac function in older animals.

Aging↗
PubMed1991

Beta-adrenergic function in aging. Basic mechanisms and clinical implications.

Catecholamines have an important endocrine and neuroendocrine role in mediating a variety of autonomic functions. One consequence of normal aging, in particular in the cardiovascular system, is a decline in beta-adrenergic function associated with an alteration in responsiveness to beta-adrenergic therapy. The intrinsic ability for muscle contractility or relaxation is maintained with age and there appears to be an alteration in the process linking the receptor with the contractile or relaxation mechanisms. In rats, beta-adrenergic receptor density decreases with age in adipose tissues and most brain areas, is unchanged in lymphocytes, heart and lung, and increases in the liver. In humans, there are no receptor changes with age in either lymphocytes or brain. In contrast, the number of high-affinity receptors (or coupled receptors) decreases with age in most tissues. In addition, there is a decrease in membrane adenylate cyclase activity or cellular production of cyclic adenosine monophosphate (adenosine 3',5'-cyclic phosphate; cAMP). Plasma noradrenaline (norepinephrine) concentration increases with age. The reduced receptor number in some tissues (down-regulation), the reduced high-affinity receptors and the reduced hormone-stimulated adenylate cyclase activity with age suggests receptor desensitisation to increased plasma noradrenaline concentration. The inability of older animals to desensitise to beta-adrenergic agonists further supports this hypothesis. However, there is an additional post-receptor reduction in catalytic unit activity with age independent of desensitisation. Medications directed at the beta-adrenergic system are commonly used in the elderly. Many of the data on the impact of age on clinical responses are conflicting or unavailable. Concomitant disease, functional status, nutritional state and polypharmacy may play an even greater role than age. However, the available data can be used to guide the selection of therapy, anticipate side effects, and predict potential interactions with other medications and diseases.

Aged↗
PubMed1990

Action of potassium on neurochemical transmission at the cardiac adrenergic neuroeffector junction with aging.

The effect of age on potassium (K+)-induced norepinephrine release in the heart was studied in 6- and 24-month-old male Fischer-344 rats. Isolated hearts were perfused with Krebs-Ringer solution according to Langendorff method. K+ was employed as 2 ml bolus at the concentrations, of 70, 90, 100 and 120 microM. Norepinephrine content was measured by high pressure liquid-chromatography/electrochemical detection methodology. At each of the K- concentrations, the amount of norepinephrine released from preparations of 6-month-old animals was significantly greater than observed from preparations of 24-month-old animals. Since K(+)-induced release of norepinephrine is associated with calcium influx, the decrease in the capacity of K+ to cause norepinephrine release with age supports the hyothesis that diminution in transmitter release is due to altered calcium function.

Age Factors↗
PubMed1990

The effect of dilevalol on cardiac autonomic neural discharge, plasma catecholamines, and myocardial beta receptor density associated with coronary occlusion.

Cats anesthetized with alpha chloralose received saline or dilevalol (1 mg/kg, IV) during a 10-minute infusion. Fifteen minutes later, the left anterior descending coronary artery was subjected to coronary occlusion 2 mm below its origin. Regional differences in the beta receptor densities were found for the atria and ventricles and for the areas within the left ventricle in cats with no coronary occlusion and dilevalol or saline. The variation in beta receptor density distribution may be related to functional differences. Coronary occlusion and saline or dilevalol did not modify the myocardial beta receptor density regional distribution. Mean times to arrhythmia and death in five saline cats were 5.8 +/- 3.6 (N = 3) and 5.4 (N = 2) minutes; three cats were killed 6 hours after coronary occlusion. In five dilevalol cats the times to arrhythmia and death were 2.2 +/- 0.8 (N = 5) and 75.9 +/- 70.7 (N = 4); 1 cat was killed. Dilevalol induced a significant decrease in blood pressure and heart rate prior to coronary occlusion. Coronary occlusion decreased blood pressure and heart rate in both groups. Twenty-five minutes after dilevalol but prior to coronary occlusion, postganglionic cardiac sympathetic neural discharge decreased to 81%. In the minutes prior to arrhythmia, postganglionic cardiac sympathetic neural discharge was 95% and was significantly increased to 121% 3 minutes after coronary occlusion. The postganglionic cardiac sympathetic neural discharge values after coronary occlusion were similar to those in the saline cats. Dilevalol depressed postganglionic cardiac sympathetic neural discharge prior to coronary occlusion but did not prevent the nonuniform (i.e., increases, decreases, or no change) discharge in the postganglionic cardiac sympathetic neural discharge associated with coronary occlusion-induced arrhythmia. Norepinephrine and epinephrine values in saline cats increased the first 5 minutes after coronary occlusion; this increase was associated with arrhythmia. Norepinephrine and epinephrine values from minute 15 to minute 360 did not differ from control. Dilevalol prevented the increase in norepinephrine and epinephrine levels associated with arrhythmia and death.

Adrenergic beta-Antagonists↗
PubMed1990

Protection against tobacco mosaic virus infection in transgenic plants requires accumulation of coat protein rather than coat protein RNA sequences.

Transgenic tobacco plants which express a chimeric gene encoding the tobacco mosaic virus (TMV) coat protein (CP) and the TMV 3' untranslated region are protected against infection by TMV. In this study chimeric genes that encode the sequences representing the TMV CP subgenomic RNA, but do not produce protein (because of removal of the initiation codon), and RNA that lacks the tRNA-like sequence of the TMV 3' end were expressed in transgenic plants. Only plants that accumulated CP, regardless of the presence of absence of the 3' end of TMV-RNA, were protected against infection by TMV. The results indicate that the CP per se, rather than TMV RNA, is responsible for the resistance to infection by TMV. Furthermore, the degree of protection is dependent upon the level of accumulated CP.

Base Sequence↗
PubMed1990

Effect of age on upregulation of the cardiac adrenergic beta receptors.

Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors.

Adrenergic beta-Antagonists↗