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PubMed2004

Low yield of ancillary diagnostic studies in neonates infected with Candida.

BACKGROUND: Fungal infection can be a significant complication for the critically ill neonate. However, the usefulness of extensive radiologic and ophthalmologic investigations in this population has not been thoroughly elucidated. OBJECTIVE: To report the incidence of organ fungal involvement diagnosed by ancillary testing (echocardiogram, ophthalmologic examination, brain imaging, and renal ultrasound (RUS)) among neonatal intensive care unit (NICU) patients with Candida infection. METHODS: This was a single center review of all NICU patients with Candida-positive cultures of blood, urine, peritoneal fluid, endotracheal tube aspirate, or cerebrospinal fluid from January 1, 1997 to June 1 2002. Data regarding the number of positive cultures, species isolated, and presence of specific risk factors and clinical symptoms were recorded for each case, as well as occurrence, timing and results of ancillary testing. RESULTS: In all, 66 patients had at least one positive culture for Candida. The majority (71%) were <1500 g at birth, and mean gestational age was 29.5+/-5.6 weeks. Echocardiograms were obtained in 54/66 (82%), and ophthalmology examinations were obtained in 36/66 (55%); none of these was consistent with fungal involvement. Brain imaging was performed in 50/66 (76%), only one of which was positive, in a patient with 16 positive blood cultures for Candida albicans. RUS were performed in 58/66 (88%) of patients, with concerning findings for fungal involvement in seven of the studies. RUS findings alone did not appear to consistently influence the length of therapy. CONCLUSIONS: Ancillary evaluations to investigate for fungal dissemination were undertaken frequently, but were of overall low yield. Although ancillary testing may be of limited additional value in centers with a low threshold for suspecting fungal infections and an aggressive approach to therapy, potentially important findings, which could impact management, may occur.

Brain↗
PubMedDate not supplied

Effect of in situ composting on reducing offensive odors and volatile organic compounds in swineries.

Seven swine farms were studied to find out how the in situ composting system, compared to the slatted floor pit system, influences the concentration and occurrence of malodorous compounds. Ammonia concentrations were measured with diffusion tubes. Small molecular sulfur compounds were analyzed using laminated bags and a gas chromatograph with a FP-detector. All other volatile organic compounds were analyzed by gas chromatography/mass spectrometry with simultaneous sniffing of the eluted compounds. About 400 organic compounds were identified from the air samples, and 94 suspect odorous compounds are listed in the present article. The most intense and unpleasant odors were caused by p-cresol, carboxylic acids (C2-C7), and some ketones such as 3-hydroxy-2-butanone, 2,3-butanedione, and 2-butanone. Terpenes (alpha-pinene, beta-pinene, 3-carene, and limonene), which originate from sawdust, caused the main peaks in the chromatograms of compost swineries. In swine confinement buildings where the composting system was functioning properly, the concentration of sulfur compounds, and especially of carboxylic acids, ketones, and p-cresol, fell effectively. The use of sawdust as composting material caused elevated concentrations of terpenes in the ambient air. There was clearly less airborne ammonia and hydrogen sulfide in the well-functioning compost swineries than in the poorly functioning ones. Elevated hydrogen sulfide levels were measured during turning work, however. In one composting swinery, the hydrogen sulfide level was as high as 15 mg/m3 during turning work. All the other concentrations of odorous compounds did not exceed occupational exposure limit values, but several compounds exceeded the respective threshold odor concentrations.

Air Pollutants, Occupational↗
PubMed2006

An elastically tethered viscous load imposes a regular gait on the motion of myosin-V. Simulation of the effect of transient force relaxation on a stochastic process.

Myosin-V is a processive molecular motor that moves membrane vesicles along actin tracks. In the simple model for motor and cargo motion investigated here, an elastic connection between motor and cargo transiently absorbs the abrupt mechanical transitions of the motor, and allows smooth relaxation of the cargo to a new position. We use a stochastic description to model motor stepping, with kinetics that depends on the instantaneous force exerted on the motor through the elastic connection. Tether relaxation is modelled as a continuous process, in which the rate is determined by the viscous drag of the cargo and the stiffness profile of the connection. Quantitative combined stochastic-continuous simulation of the dynamics of this system shows that bulky loads can impose a highly regular gait on the motor. If the characteristics of the elastic connection are similar to those of the myosin-II coiled-coil domain, the myosin-V motor, tether and cargo form a true escapement, in which the motor only escapes from its current position after one or more force thresholds have been crossed. Multiple thresholds limit the variation in tether length to values below that of the total step size.

Actins↗
PubMedDate not supplied

Special assessment of aircraft noise effects during night by the Council of Experts for Environmental Questions of FRG.

The "Special Assessment of Environment and Health" (SAEH) by the Council of Experts for Environmental Questions of Federal Republic of Germany is presented regarding to it's statements concerning the consequences of aircraft noise during night. Considering the issue of sustainability it is emphasized that lower limit values of the validity of scientific results need to be accepted. As the discussion of the literature shows the statements of the Council are rather vague and warily. This is a question of used parameters of noise effects during the night as well as its interpretation. It seems necessary to utilize a hierarchical structure of limit values and with interpretation of the term "threshold" as normal physiological reactions. More investigations are necessary in this field.

Advisory Committees↗
PubMedDate not supplied

Hypertension and diabetes mellitus: the critical role of evidence based decision making in patient management.

Many diabetic hypertensives are inadequately managed because of the doctor's misplaced emphasis on possible differences in efficacy and risk profile of antihypertensive drugs. These patients are at higher risk of various cardiovascular events, and evidence shows they experience greater reduction in adverse clinical outcomes as a result of tight control of blood pressure than do nondiabetic hypertensives. It is, therefore, critically important that such patients be identified and that the blood pressure is tightly treated. Several drugs often have to be used in combination in order to achieve adequate blood pressure control. Nonpharmacologic measures, such as exercise, have been shown to reduce blood pressure and to reduce the rate complications in diabetic patients. All classes of antihypertensives have been shown to be equivalent in reducing all adverse cardiovascular events in diabetic hypertensives. Although there is nothing to choose between diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, the choice of drug should be tailored for the individual patient. Drug selection should be based on the complication that is most likely in the given patient. Available data suggests that the lower the blood pressure the better the prognoses, with no threshold of the lower limit of the ideal value. Many professional associations advise that a target blood pressure in the diabetic hypertensive under treatment should be below 130/80 mm Hg. There is no evidence to support the avoidance of thiazide diuretics in these patients, and indeed some patients derive specific benefits from the use of these drugs. Tight control of blood pressure is the overriding priority, and this takes precedence over the theoretical debate of which drug is the best choice or concern over possible adverse reactions.

Clinical Trials as Topic↗
PubMed1986

Exercise testing after correction of tetralogy of Fallot: the fallacy of a reduced heart rate response.

Thirty-nine patients, 5 to 19 years of age, were studied 1 to 10.5 years (mean 4.5) after surgical correction of tetralogy of Fallot (TF). In 32 of them the results of an exercise performance test based on heart rate response to submaximal exercise (VO2, 170 [bpm]) was compared with another index of physical performance capacity, which is independent from heart rate: the ventilatory threshold. In patients operated for TF, the mean heart rate during exercise was significantly lower than that corresponding to the same level of exercise in normal children (p less than 0.001) and their mean VO2, 170 was normal. Theoretically, these findings could be interpreted as indicating a normal or high physical performance capacity. By contrast, the ventilatory threshold was significantly lower than that in normal children: it averaged 89.3 +/- 15.7%, 79.7 +/- 14.4%, and 88.5 +/- 15.8% of the mean value in normal children matched for age, weight, and height, respectively. More patients had a subnormal value for ventilatory threshold than for VO2, 170: 58% had a ventilatory threshold below the 95% confidence limits for age-matched normal individuals and 75% had a subnormal value when compared to weight-matched normal children. For VO2, 170, these values were 39% and 34%, respectively (p less than 0.05). We recommend the evaluation of the exercise performance capacity in patients operated for TF not only by measuring heart rate response and VO2, 170 which may be misleading because of relative bradycardia, but also by analyzing gas exchange and determining the ventilatory threshold.

Adolescent↗
PubMed2005

Toxic metal content of particulate matter (PM10), within the Greater Area of Athens.

This study presents results from a yearlong particulate matter measurement campaign, conducted across the Greater Athens Area, at four locations, between 1st June 2001 and 31st May 2002. The collected PM(10) 24-h samples were analyzed for nine toxic metals and metalloids (Pb, As, Cd, Ni, Cr, Mn, V, Cu, Hg). Concerning the five elements regulated by the European Union, annual average concentrations of Pb were found below the limit values at all sites, Cd and Ni concentrations were lower than the prospective assessment thresholds at all sites, concentrations of As exceeded the assessment threshold at two sites, while concentrations of Hg were found below detection limits in all samples. Concentration levels of Mn and V were in compliance with the values proposed by the World Health Organization. The seasonal and spatial variability of metal concentrations was examined and site-specific correlation analysis was conducted for the identification of metals with similar origin. The association between trace metals and NO(x) concentrations was explored to account for the impact of automotive sources, at two traffic-impacted sites. Cu was the metal most closely linked with the road transport sector. The relation of concentration levels with the prevalence of winds from different sectors was studied in an effort to investigate the transport of metal particles from various zones of the city. Finally, factor analysis was carried out to extract the main components responsible for the variance of the dataset and to attribute them to specific source categories, with vehicle-related sources being important in all cases.

Air Pollutants↗
PubMed1991

Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy.

Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients. Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring. The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours. Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect. The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect. When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect. In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative. Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation.

Aged↗
PubMed2000

Normative values for female genital sensation.

OBJECTIVES: Neurologic disorders might be responsible for many cases of female sexual dysfunction. Yet, they are currently undiagnosed because of the lack of measurement tools to assess genital neural function. Therefore, our objective is to provide norms for sensory thresholds in the vagina and clitoris, for a wide range of patient ages. METHODS: Vaginal and clitoral warm, cold, and vibratory sensory thresholds were measured in 89 healthy paid volunteers by the method of limits. Normograms were derived from this group of healthy volunteers. An additional 61 patients were also tested, for a total of 150 individuals. Sixty-two individuals (42 healthy volunteers and 20 patients) from the total group were tested twice to provide test-to-test repeatability data across the range of clinical (normal and abnormal) responses. RESULTS: Normograms are presented, providing age-corrected upper and lower normal values, expressed as 95% confidence limits for warm, cold, and vibratory thresholds. Intertest repeatability is also reported. CONCLUSIONS: Thermal and vibratory thresholds of both the vaginal and clitoral region are clinically feasible, valid, and repeatable. These can be applied as a valuable diagnostic tool to assess neural dysfunction through sensory assessment of the female genitalia.

Adolescent↗
PubMedDate not supplied

Household appliance use and residential exposure to 60-hz magnetic fields.

We characterized the distribution of exposure to magnetic fields (MFs) during daily activities and during household appliance use, and estimated the relative contribution of various activities and appliances to total daily exposure. One hundred sixty-two subjects provided information on their patterns of appliance use and wore personal monitors for 24 h to collect MF exposure data. Of total exposure, 27% accumulated while subjects were in bed; 41% while at home but not in bed; 9% at work; and 24% elsewhere. Less than 2% of the total MF exposure accumulated during the use of each of the eight individual appliances considered, except computers, during the use of which 9% of the total exposure accumulated. Of the time subjects spent at exposure levels higher than 2 microT, 8% accumulated while they were using microwave ovens, and 4% and 3% while using computers and electric stoves, respectively. Mean MF measurements tended to be lowest when subjects were in bed and highest at work and during the use of microwave ovens, coffee grinders, hair dryers, and electric shavers. Results from questionnaires on household appliance use in the past year were not useful in predicting the total mean exposure level and over-threshold exposures measured by 24-h personal monitors. Significant MF exposure accumulates at home, at work, and elsewhere; therefore, accurate exposure assessment needs to consider residential, occupational, and other sources together. Questionnaire-based information on appliance use has limited value in the assessment of average and over-threshold exposure to MFs.

Activities of Daily Living↗
PubMed1999

Customer exposure to MTBE, TAME, C6 alkyl methyl ethers, and benzene during gasoline refueling.

We studied customer exposure during refueling by collecting air samples from customers' breathing zone. The measurements were carried out during 4 days in summer 1996 at two Finnish self-service gasoline stations with "stage I" vapor recovery systems. The 95-RON (research octane number) gasoline contained approximately 2.7% methyl tert-butyl ether (MTBE), approximately 8.5% tert-amyl methyl ether (TAME), approximately 3.2% C6 alkyl methyl ethers (C6 AMEs), and 0.75% benzene. The individual exposure concentrations showed a wide log-normal distribution, with low exposures being the most frequent. In over 90% of the samples, the concentration of MTBE was higher (range <0.02-51 mg/m3) than that of TAME. The MTBE values were well below the short-term (15 min) threshold limits set for occupational exposure (250-360 mg/m3). At station A, the geometric mean concentrations in individual samples were 3.9 mg/m3 MTBE and 2. 2 mg/m3 TAME. The corresponding values at station B were 2.4 and 1.7 mg/m3, respectively. The average refueling (sampling) time was 63 sec at station A and 74 sec at station B. No statistically significant difference was observed in customer exposures between the two service stations. The overall geometric means (n = 167) for an adjusted 1-min refueling time were 3.3 mg/m3 MTBE and 1.9 mg/m3 TAME. Each day an integrated breathing zone sample was also collected, corresponding to an arithmetic mean of 20-21 refuelings. The overall arithmetic mean concentrations in the integrated samples (n = 8) were 0.90 mg/m3 for benzene and 0.56 mg/m3 for C6 AMEs calculated as a group. Mean MTBE concentrations in ambient air (a stationary point in the middle of the pump island) were 0.16 mg/m3 for station A and 0.07 mg/m3 for station B. The mean ambient concentrations of TAME, C6 AMEs, and benzene were 0.031 mg/m3, approximately 0.005 mg/m3, and approximately 0.01 mg/m3, respectively, at both stations. The mean wind speed was 1.4 m/sec and mean air temperature was 21 degreesC. Of the gasoline refueled during the study, 75% was 95 grade and 25% was 98/99 grade, with an oxygenate (MTBE) content of 12.2%.

Air Pollutants↗
PubMed2004

Registering the response of tissues exposed to an interferential electric current stimulation.

Electrotherapy is a treatment method in which an electric stimulus is used to achieve physiological changes in the body. When increasing the level of the electric stimulus, three sensory, three motor and a pain response can be found. In this paper the three sensory threshold levels (1st just noticeable weak tingling sensation, 2nd a very fine but definite tingling and 3rd moderate strong tingling) were studied with an interferential electric current stimulus. The interferential electric current can be achieved by summing two alternating currents with little different frequencies with each other. As a current source, the study used a value intended for interferential electric current therapy. The threshold value measurements were performed on 5 days to 6 volunteers. The method of limits is a frequently used technique for determining sensory thresholds where ascending or descending stimuli is used and the observer reports of the appearance or disappearance of the sensation, respectively. A Bekesy's algorithm is a threshold tracking method with a variable stimulus. They were used for controlling the interferential electric current stimulus, and hence, for studying the,thresholds. By using the method of limits, the measurements were done at three sensory threshold levels at interferential frequencies deltaf of 10 Hz, 30 Hz, 50 Hz, and 100 Hz caused by two sine waves, one with a frequency between 2490 Hz and 2400 Hz, and the other constant 2500 Hz. In the method based on Bekésy's algorithm the interferential frequency deltaf was increased from 1 Hz to 100 Hz by changing the first frequency from 2499 Hz to 2400 Hz and the measurement was repeated for all three sensory thresholds. The sensory thresholds for interferential current stimuli seem to be quite unaffected by the interferential electric current frequency among the healthy test persons, and no distinct interferential electric current frequencies at which the threshold values should be measured were found in this study.

Adult↗
PubMed1996

Electroconvulsive therapy and resistant depression: clinical implications of seizure threshold.

BACKGROUND: Patients with major depressive disorder (MDD) were treated with electroconvulsive therapy (ECT) to determine (1) variability of initial seizure threshold, (2) factors that influence seizure threshold, (3) change in seizure threshold during the ECT course, and (4) relationship of seizure threshold to antidepressant effects. METHOD: Seizure threshold was measured by a stimulus titration technique during the first, eighth, and final ECT of medication-free patients who had MDD, endogenous subtype based on Research Diagnostic Criteria and were randomly assigned to three-times-weekly, bilateral, brief pulse ECT (N = 24) or twice-weekly ECT plus one simulated treatment per week (N = 23). Subsequent to the first ECT, stimulus intensity was 1.3 to 1.8 (median = 1.5) times threshold. The Hamilton Rating Scale for Depression (HAM-D) was the primary clinical outcome measure. RESULTS: Initial seizure threshold varied by 594%. Gender (p = .03), total strength of pre-ECT pharmacotherapy trials (p = .02), and age (p = .12) accounted for 23.9% of the variance. Threshold increased by 42% +/- 26% (p = .0001) from the first to the final ECT, and seizure duration decreased by 33% +/- 28% (p = .0001). Seizure duration and mean stimulus intensity were negatively associated over all treatments (r = -.49, p = .0003). Change in HAM-D score was related to duration of the current depressive episode (r = -.39, p = .006) and total strength of pre-ECT pharmacotherapy trials (r = -.39, p = .008), but not to seizure threshold or duration. CONCLUSION: (1) Initial seizure threshold for pulse bilateral ECT is highly variable and not yet amenable to accurate prediction. (2) Stimulus titration allows threshold to be determined on an individual basis and dosage for subsequent treatments to be defined. (3) Seizure duration is of limited value as a sole criterion for the adequacy of treatment when initial threshold is unknown and/or electrical doses that substantially exceed threshold are used. (4) With moderately suprathreshold bilateral ECT, a relationship of seizure threshold to antidepressant response is not demonstrable.

Adult↗
PubMed2004

Establishing normal hearing with the dichotic multiple-frequency auditory steady-state response compared to an auditory brainstem response protocol.

OBJECTIVE: To determine the clinical usefulness of the dichotic multiple-frequency (MF) auditory steady-state response (ASSR) technique for estimating normal hearing compared to a 0.5-kHz tone burst and broadband click auditory brainstem response (ABR) protocol in a sample of adults. MATERIAL AND METHODS: A comparative experimental research design was selected in order to compare estimations of normal hearing obtained with the dichotic ASSR technique at 0.5, 1, 2 and 4 kHz with a 0.5-kHz tone burst and broadband click ABR protocol. The recording times required for each procedure were also compared. Normal-hearing subjects (n = 28) were selected according to immittance values within normal limits and pure-tone behavioural thresholds of < 25 dB HL across frequencies. RESULTS: The dichotic MF ASSR estimated normal hearing to be, on average, 30-34 dB HL across the range 0.5-4 kHz. The mean estimate of normal hearing for 0.5 kHz using tone burst ABRs was 30 dB nHL and the mean click ABR threshold was 16 dB nHL, i.e. 14-18 dB better than the ASSR thresholds. The dichotic MFASSR technique recorded 8 thresholds (4 in each ear) in a mean time of 23 min. The ABR protocol recorded 4 thresholds (2 in each ear) in a mean time of 25 min. CONCLUSION: Both the dichotic MF ASSR and ABR protocols provided a time-efficient estimation of normal hearing. There was no significant difference between the tone burst ABR and MF ASSR techniques in terms of estimation of normal hearing at 0.5 kHz. The dichotic MF ASSR technique proved more time-efficient by determining more thresholds in a shorter time compared to the ABR protocol.

Adolescent↗
PubMed2004

Accuracy limitations of chronaxie values.

The strength-duration curve is a plot of the threshold current (I) versus pulse duration (d) required to stimulate excitable tissue. On this curve are two points: 1) rheobase (b) and 2) chronaxie (c). Rheobase is the threshold current for an infinitely long-duration stimulus. Chronaxie, the excitability constant, is the duration of a pulse of current of twice rheobasic strength. The mathematical expression for the strength-duration curve is I = b(1 + c/d). Although there are many published values for chronaxie for various excitable tissues, the range of variability for a given tissue type is quite large. This paper identifies five factors that can affect the accuracy of chronaxie measurement and shows that the most reliable values can be obtained with a rectangular pulse delivered from a constant-current source.

Action Potentials↗
PubMed2003

Bladder-anal reflex.

AIMS: The purposes of this study were to evaluate the bladder-anal reflex (BAR) latency in asymptomatic women and determine the pathway of the reflex using selective anesthesia and neuromuscular block. METHODS: Urinary incontinence, voiding dysfunction, and pelvic organ prolapse are common problems in women. Evaluation of pelvic nerve function often augments the clinical assessment of these women. Urethral-anal and clitoral-anal reflex testing have been reported as methodologies to assess patients with neurogenic disorders. A bladder-anal reflex is also obtainable but has not been reported previously in the literature. Twenty-two subjects and two patients were recruited for evaluation of the BAR. RESULTS: This study has allowed us to estimate reference ranges for BAR latency and threshold. We defined the upper limit of these reference ranges as two standard deviations above their respective means. For the BAR latency, the upper limit of the reference range is 91 msec. Any latency value above this limit should be considered abnormal. The upper limit for the BAR threshold reference range is 37.7 mA. Lower thresholds are not thought to be clinically meaningful due to the presence of several low sensory thresholds in this asymptomatic normal population. CONCLUSIONS: The BAR was obtainable in asymptomatic women and compatible with known anatomy and innervation of the lower urinary tract.

Adult↗
PubMed2006

A novel generic dipstick-based technology for rapid and precise detection of tetracycline, streptogramin and macrolide antibiotics in food samples.

Excessive use of antibiotics in veterinary medicine and as growth promoters in stock farming has been associated with the dramatically increasing prevalence of multidrug-resistant human pathogenic bacteria. European community legislators have therefore restricted the veterinary use of antibiotics and banned them as growth-promoting food additives in stock breeding (1831/2003/EC). The monitoring of such legislation requires technology for precise and straightforward on-site quantification of antibiotics in farm samples and food products without the need for extensive laboratory equipment and trained personnel. Capitalizing on bacterial transcriptional regulators (TetR, PIP, E), which are dose-dependently released from their cognate operators (tetO, PIR, ETR) upon binding of specific classes of antibiotics (tetracycline, streptogramins, macrolides) we have designed an easy-to-handle dipstick-based assay for detection of antibiotic levels in serum, meat and milk whose detection limits are up to 40-fold below licensed threshold values. The generic dipstick consists of either nitrocellulose, nylon or polyvinylidenfluorid (PVDF) membrane strips coated with streptavidin and immobilized biotinylated operator DNA, which acts as capture DNA to bind hexa-histidine (His(6))-tagged bacterial biosensors. Antibiotics present in specific samples triggered the dose-dependent release of the capture DNA-biosensor interaction, which, after dipping into two different solutions, results in a correlated conversion of a chromogenic substrate by a standard His(6)-targeted enzyme complex. This can be quantified by comparison of the dipstick to a standardized color scale or by assessing the terminal solution at 450nm. As demonstrated using serum, meat and milk samples spiked with 14 different antibiotics, the dipstick technology provided sensitive detection in a rapid assay format, and could be employed to monitor non-authorized use of antibiotics and to discover novel antibiotics.

Animals↗
PubMed2005

The multifarious short-term regulation of ammonium assimilation of Escherichia coli: dissection using an in silico replica.

Ammonium assimilation in Escherichia coli is regulated through multiple mechanisms (metabolic, signal transduction leading to covalent modification, transcription, and translation), which (in-)directly affect the activities of its two ammonium-assimilating enzymes, i.e. glutamine synthetase (GS) and glutamate dehydrogenase (GDH). Much is known about the kinetic properties of the components of the regulatory network that these enzymes are part of, but the ways in which, and the extents to which the network leads to subtle and quasi-intelligent regulation are unappreciated. To determine whether our present knowledge of the interactions between and the kinetic properties of the components of this network is complete - to the extent that when integrated in a kinetic model it suffices to calculate observed physiological behaviour - we now construct a kinetic model of this network, based on all of the kinetic data on the components that is available in the literature. We use this model to analyse regulation of ammonium assimilation at various carbon statuses for cells that have adapted to low and high ammonium concentrations. We show how a sudden increase in ammonium availability brings about a rapid redirection of the ammonium assimilation flux from GS/glutamate synthase (GOGAT) to GDH. The extent of redistribution depends on the nitrogen and carbon status of the cell. We develop a method to quantify the relative importance of the various regulators in the network. We find the importance is shared among regulators. We confirm that the adenylylation state of GS is the major regulator but that a total of 40% of the regulation is mediated by ADP (22%), glutamate (10%), glutamine (7%) and ATP (1%). The total steady-state ammonium assimilation flux is remarkably robust against changes in the ammonium concentration, but the fluxes through GS and GDH are completely nonrobust. Gene expression of GOGAT above a threshold value makes expression of GS under ammonium-limited conditions, and of GDH under glucose-limited conditions, sufficient for ammonium assimilation.

Adenosine Diphosphate↗