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Biomedical subjects

J D Cohen

Publications and source records attributed to J D Cohen.

At least 145 records · Page 8Linked to original sources

Regulation of indole-3-acetic Acid biosynthetic pathways in carrot cell cultures.

2,4-Dichlorophenoxyacetic acid (2,4-D) promotes the accumulation of tryptophan-derived indole-3-acetic acid (IAA) in carrot cell cultures during callus proliferation by a biosynthetic pathway that is apparently not active during somatic embryo formation. The effects of 2,4-D were examined by measuring the isotopic enrichment of IAA due to the incorporation of stable isotope-labeled precursors (deuterium oxide, [(15)N]indole, and (2)H(5)-l-tryptophan). Enrichment of IAA from deuterium oxide is similar in both cultured hypocotyls and cell suspension cultures in the presence and absence of 2,4-D, despite the large differences in absolute IAA concentrations. The enrichment of IAA due to the incorporation of [(15)N]indole is also similar in callus proliferating in the presence of 2,4-D and in embryos developing in the absence of 2,4-D. The incorporation of (2)H(5)-l-tryptophan into IAA, however, is at least 7-fold higher in carrot callus cultures proliferating in the presence of 2,4-D than in embryos developing in the absence of 2,4-D. Other experiments demonstrated that this differential incorporation of (2)H(5)-l-tryptophan into IAA does not result from differential tryptophan uptake or its subsequent compartmentation. Thus, it appears that differential pathways for IAA synthesis operate in callus cultures and in developing embryos, which may suggest that a relationship exists between the route of IAA biosynthesis and development.

Journal Article↗

Amide-Linked Indoleacetic Acid Conjugates May Control Levels of Indoleacetic Acid in Germinating Seedlings of Phaseolus vulgaris.

We have shown that amide-linked IAA (indole-3-acetic acid) conjugates accumulated to high levels during maturation of bean seeds (K. Bialek and J.D. Cohen [1989] Plant Physiol 91: 775-779). In the present study, we were interested in the fate of these and other IAA conjugates during seed germination. The content of amide-linked conjugates of IAA in cotyledons declined dramatically during the first hours of imbibition. The rate of decline slowed markedly during the period of the resumption of axis growth. The level of amide-linked IAA conjugates in cotyledons remained relatively high after almost 1 week of germination. The decline of IAA conjugates in cotyledons was followed by a steady increase in the content of both free and amide-linked IAA in the embryonic axes. Amide-linked IAA conjugates were also present in the axes cultured on agar after the cotyledons were removed, which suggests that de novo production of these IAA conjugates occurs in the axis of germinating bean seedlings. A comparison of relative amounts of free and conjugated IAA in the axes of intact seedlings and axes cultured on agar showed lower levels of free IAA and higher levels of conjugated IAA in much slower growing isolated axes. These results suggest a more general role for IAA conjugates in the control of seedling growth than simply to serve as a seed storage form of auxin.

Journal Article↗

Comparison of Benzyl Adenine Metabolism in Two Petunia hybrida Lines Differing in Shoot Organogenesis.

The uptake and metabolism of the cytokinin benzyl adenine (BA) was compared in two lines of Petunia hybrida Vilm. differing in their shoot organogenic response. Leaf transfer experiments using shoot induction medium containing 4.4 micromolar BA showed that leaf explants from petunia line St40 required a shoot induction period of 6 to 10 days for commitment to shoot organogenesis; whereas leaf explants from petunia TLV1 required 12 to 28 days. The short induction period of petunia St40 and the higher organogenic response was positively associated with a threefold higher absorption of BA from the medium, an increased BA ribotide metabolite pool, the presence of BA within the explant during the shoot induction period, and the production of an unidentified metabolite C. However, the study of petunia TLV1 leaf explants showed that neither BA nor metabolite C are required during the shoot induction period for eventual shoot development. The longer shoot induction period of TLV1 was associated with low BA uptake during 24 days, a decreasing ribotide metabolite pool, the absence of benzyl adenosine triphosphate and metabolite C throughout the study, and the absence of BA within the explant during the shoot induction period. Differences in the shoot organogenic response of these related plant lines have been shown to be associated with differences in exogenous cytokinin uptake and the subsequent metabolism of that hormone.

Journal Article↗

Measurement of indolebutyric Acid in plant tissues by isotope dilution gas chromatography-mass spectrometry analysis.

An internal standard, [(13)C][indole-2]-indole-3-butyric acid, was synthesized from indole-2[(13)C] and was shown to be effective for the quantitative determination of indole-3-butyric acid from plant tissue. When this standard was used along with [(13)C(6)]indole-3-acetic acid, both indolic auxins could be quantified from the same tobacco (Nicotiana tabacam) leaf sample by isotope dilution analysis using selected ion monitoring gas chromatography-mass spectrometry for detection.

Journal Article↗

Smoking is a risk factor for coronary spasm in young women.

BACKGROUND: Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease. METHODS AND RESULTS: We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1. CONCLUSIONS: These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.

Adult↗

A parallel distributed processing approach to automaticity.

We consider how a particular set of information processing principles, developed within the parallel distributed processing (PDP) framework, can address issues concerning automaticity. These principles include graded, activation-based processing that is subject to attentional modulation; incremental, connection-based learning; and interactivity and competition in processing. We show how simulation models, based on these principles, can account for the major phenomena associated with automaticity, as well as many of those that have been troublesome for more traditional theories. In particular, we show how the PDP framework provides an alternative to the usual dichotomy between automatic and controlled processing and can explain the relative nature of automaticity as well as the fact that seemingly automatic processes can be influenced by attention. We also discuss how this framework can provide insight into the role that bidirectional influences play in processing: that is, how attention can influence processing at the same time that processing influences attention. Simulation models of the Stroop color-word task and the Eriksen response-competition task are described that help illustrate the application of the principles to performance in specific behavioral tasks.

Association Learning↗

Effect of hyperthermia in vitro and in vivo on adenine and pyridine nucleotide pools in human peripheral lymphocytes.

Hyperthermia has been shown in vitro and in vivo to potentiate the effects of ionizing irradiation. Previous studies found that hyperthermia alters the metabolism of adenosine diphosphate (ADP)-ribose polymers required for recovery from DNA damage and that poly(ADP-ribose) polymerase activity is very sensitive to cellular nicotinamide-adenine dinucleotide (NAD) levels. Thus, the effect of 41.8 degrees C hyperthermia in vitro and in vivo on NAD and adenosine triphosphate (ATP) levels was studied in human peripheral lymphocytes. In vitro studies showed significant decreases in oxidized NAD (NAD+) and ATP levels after heating that simulated a clinical whole-body hyperthermia (WBH) treatment. This nucleotide depletion could not be attributed to nucleotide leakage or increased enzymatic NAD+ consumption. As the reduction of NAD observed was sufficient to decrease poly(ADP-ribose)polymerase activity by 50%, the studies were extended to clinica cases. Cellular NAD+ and ATP were measured in previously stored lymphocytes obtained from four patients before and after WBH; a statistically significant decrease in NAD+ was observed after WBH which quantitatively agreed with the in vitro results. Based on these results a prospective study was done in three patients; NAD+ was extracted immediately on sample collection, and the kinetics of WBH-induced NAD depletion were studied. These data, which agree quantitatively with the laboratory results, are presented.

Adenosine Triphosphate↗

Managing the whole patient with hypertension: practical applications in a clinical setting.

Physicians are aware of the value of treating hypertension. Complications such as stroke and congestive heart failure are less likely to occur in the well-controlled patient. In our quest to add coronary heart disease to this list, we must go beyond simple reduction of blood pressure. We must consider other risk factors such as hypercholesterolemia, cigarette smoking, diabetes mellitus, and family history. The presence of one or more of these may indicate a more aggressive treatment approach. Similarly the presence of left ventricular hypertrophy, coronary disease, or renal disease may indicate specific pharmacotherapy. On the other hand, the low-risk patient with no other problems or conditions may be treated with only nonpharmacologic therapy such as weight loss, dietary sodium reduction, and/or alcohol restriction. Every patient has a different constellation of findings. Every patient should be treated individually. It is no longer sufficient just to lower blood pressure; we need to manage the whole patient with hypertension; keeping in mind that most antihypertensive agents are equally effective, the side effect profile is often the decisive factor in choosing an antihypertensive agent.

Adult↗

Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents.

This open, multicenter phase III study was designed to assess the efficacy and long-term safety of terazosin (1 to 40 mg/day), alone or in combination with other antihypertensive drugs, in 364 patients with mild to moderate essential hypertension. Compared with baseline values, long-term terazosin monotherapy or combination therapy resulted in consistent decreases in both systolic and diastolic blood pressures, with a mean reduction in supine diastolic pressure of 12 to 14 mm Hg. The numbers of patients with controlled blood pressure at the last evaluable visit of each therapy period were as follows: terazosin alone, 106 of 245 (43%); terazosin with added diuretic, 70 of 112 (63%); diuretic with added terazosin, 47 of 88 (53%); and terazosin plus diuretic with added beta-blocker, 22 of 32 (69%). Most adverse events were mild or moderate in severity. Only pain in extremities had a higher incidence during long-term treatment (6%, 181 to 360-day period) than during initial short-term treatment (5%, 1 to 90-day period). Three of six syncopal events occurred during the initial 180 days of treatment; this 0.8% (3/364) incidence was comparable with that reported previously for short-term studies. Only one case of syncope occurred during terazosin monotherapy. Terazosin was judged to be a safe and effective long-term medication for the treatment of hypertension.

Adrenergic alpha-Antagonists↗

Thymidine-cisplatin vs thymidine-carboplatin interactions in human T-cell acute leukemia.

Thymidine is shown to sensitize JM human T-cell acute leukemia cells to cisplatin killing in vitro with dose modifying factors of 1.72, 1.62, and 1.76 at 200, 500, and 1000 micrograms thymidine/ml x 24 h. The magnitude of thymidine-cisplatin sensitization increases with longer thymidine exposures (500 micrograms/ml) up to 16 h but is not further increased at 24 h. For a 25 h thymidine exposure, enhancement is greater for cisplatin (3 micrograms/ml x 1 h) starting 12-24 h into the thymidine exposure vs starting at 0-8 h (p less than or equal to 0.0004). Results are precisely the same for simultaneous studies using carboplatin except that (1) thymidine enhances carboplatin cytotoxicity more than cisplatin killing, (2) enhancement of carboplatin killing varies little with the timing of carboplatin administration during a 25 h thymidine exposure. These findings are discussed relative to their clinical applicability.

Carboplatin↗

Trials of hypertension prevention. Phase I design.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

Adult↗

Echocardiographic evaluation of cardiac structure and function in elderly subjects with isolated systolic hypertension.

One hundred four participants in the Systolic Hypertension in the Elderly Program (SHEP) trial (mean age 71 +/- 6 years) were examined by Doppler echocardiography to gain information on the cardiac structural and functional alterations in isolated systolic hypertension. Participants had a systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg and were compared with 55 age-matched normotensive control subjects. Left ventricular mass index was significantly higher in the participants than in the normotensive subjects (103 +/- 28 versus 87 +/- 23 g/m2, p = 0.0014) and 26% of the participants met echocardiographic criteria for left ventricular hypertrophy compared with 10% of normotensive subjects. Left atrial index was also greater in participants than in normotensive subjects (2.26 +/- 0.32 versus 2.11 +/- 0.24 cm/m2, p = 0.005) and 51% of participants had left atrial enlargement. Doppler measures of diastolic filling were significantly different between the two groups, with peak atrial velocity higher (76 +/- 17 versus 69 +/- 17 cm/s, p = 0.02) and ratio of peak early to atrial velocity lower (0.76 +/- 0.23 versus 0.86 +/- 0.22, p = 0.0124) in participants. There was no correlation between left ventricular mass index and Doppler measures of diastolic function, but relative wall thickness correlated significantly with peak atrial velocity (r = 0.22, p = 0.016) and peak early to peak atrial velocity ratio (r = 0.24, p = 0.007). There was no difference in M-mode ejection phase indexes of systolic performance (shortening fraction and peak velocity of circumferential fiber shortening) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy.

The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗

Stable Isotope Labeling, in Vivo, of d- and l-Tryptophan Pools in Lemna gibba and the Low Incorporation of Label into Indole-3-Acetic Acid.

We present evidence that the role of tryptophan and other potential intermediates in the pathways that could lead to indole derivatives needs to be reexamined. Two lines of Lemna gibba were tested for uptake of [(15)N-indole]-labeled tryptophan isomers and incorporation of that label into free indole-3-acetic acid (IAA). Both lines required levels of l-[(15)N]tryptophan 2 to 3 orders of magnitude over endogenous levels in order to obtain measurable incorporation of label into IAA. Labeled l-tryptophan was extractable from plant tissue after feeding and showed no measurable isomerization into d-tryptophan. d-[(15)N]tryptophan supplied to Lemna at rates of approximately 400 times excess of endogenous d-tryptophan levels (to yield an isotopic enrichment equal to that which allowed detection of the incorporation of l-tryptophan into IAA), did not result in measurable incorporation of label into free IAA. These results demonstrate that l-tryptophan is a more direct precursor to IAA than the d isomer and suggest (a) that the availability of tryptophan in vivo is not a limiting factor in the biosynthesis of IAA, thus implying that other regulatory mechanisms are in operation and (b) that l-tryptophan also may not be a primary precursor to IAA in plants.

Journal Article↗

Red light-regulated growth. I. Changes in the abundance of indoleacetic acid and a 22-kilodalton auxin-binding protein in the maize mesocotyl.

We examined the changes in the levels of indoleacetic acid (IAA), IAA esters, and a 22-kilodalton subunit auxin-binding protein (ABP1) in apical mesocotyl tissue of maize (Zea mays L.) during continuous red light (R) irradiation. These changes were compared with the kinetics of R-induced growth inhibition in the same tissue. Upon the onset of continuous irradiation, growth decreased in a continuous manner following a brief lag period. The decrease in growth continued for 5 hours, then remained constant at 25% of the dark rate. The abundance of ABP1 and the level of free IAA both decreased in the mesocotyl. Only the kinetics of the decrease in IAA within the apical mesocotyl correlated with the initial change in growth, although growth continued to decrease even after IAA content reached its final level, 50% of the dark control. This decrease in IAA within the mesocotyl probably occurs primarily by a change in its transport within the shoot since auxin applied as a pulse move basipetally in R-irradiated tissue at the same rate but with half the area as dark control tissue. In situ localization of auxin in etiolated maize shoots revealed that R-irradiated shoots contained less auxin in the epidermis than the dark controls. Irradiated mesocotyl grew 50% less than the dark controls even when incubated in an optimal level of auxin. However, irradiated and dark tissue contained essentially the same amount of radioactivity after incubation in [14C]IAA indicating that the light treatment does not affect the uptake into the tissue through the cut end, although it is possible that a small subset of cells within the mesocotyl is affected. These observations support the hypothesis that R causes a decrease in the level of auxin in epidermal cells of the mesocotyl, consequently constraining the growth of the entire mesocotyl.

Biological Transport↗