Showing papers by "University of Copenhagen published in 1989"

The abrupt termination of the Younger Dryas climate event

Abstract: PREVIOUS studies on two deep Greenland ice cores have shown that a long series of climate oscillations characterized the late Weichselian glaciation in the North Atlantic region1, and that the last glacial cold period, the Younger Dryas, ended abruptly 10,700 years ago2. Here we further focus on this epoch-defining event, and present detailed heavy-isotope and dust-concentration profiles which suggest that, in less than 20 years, the climate in the North Atlantic region turned into a milder and less stormy regime, as a consequence of a rapid retreat of the sea-ice cover. A warming of 7 °C in South Greenland was completed in about 50 years.

Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice.

Abstract: In patients with obstructive jaundice caused by malignant stricture of the extrahepatic bile duct we compared survival time, complication rates, hospitalisation requirements, and quality of life after palliation by endoscopic endoprosthesis or bypass surgery. During diagnostic endoscopic cholangiography 50 patients were randomised to the two treatment alternatives. All 25 patients randomised to endoprosthesis were treated by this procedure, whereas only 19 of 25 patients randomised to bypass surgery underwent operative biliary-digestive anastomosis. Life table analysis revealed no difference in survival between treatment groups or randomisation groups. No differences were found when other variables were compared. We conclude, that palliation of obstructive jaundice in malignant bile duct obstruction with endoscopically introduced endoprosthesis is as effective as operative bypass.

The origin of Arctic precipitation under present and glacial conditions

Abstract: At low altitude locations, the deuterium excess d = δ D - 8δ 18 O in precipitation generally varies with the season in antiphase with the δ's. In the high-altitude regions of the Greenland ice sheet, however, d in the snow varies with only a few months time lag behind the δ's. A model for d values in Greenland precipitation is developed on the basis of Rayleigh condensation/sublimation with due account taken of kinetic effects during both evaporation of sea water and sublimation. The model predicts that the initial mixing ratio w so in precipitating air determines the slope of the d versus δ relationship at late stages of the precipitation process, and that the sea surface temperature T s in the source area of the moisture only influences the d level. The generally high d -values in ice sheet precipitation are compatible only with high values of W so and T s , which suggests the subtropical part of the North Atlantic Ocean as a dominating moisture source for ice sheet precipitation. This is supported experimentally: when the model is run with monthly W so and T s mean values oberved at Ship E (35° N, 48° W), it reproduces the high d level, the amplitude of the seasonal d variations, and the few months phase difference between d and δ on the ice sheet. None of these features can be reproduced with a local, high-latitude moisture source. Detailed isotope analyses of ice core increments, spanning several abrupt climatic shifts under glacial conditions, show close to present d values during the cold phases, but lower d values during the mild phases. This feature is discussed in the light of the model experiments. DOI: 10.1111/j.1600-0889.1989.tb00321.x

Serotonin-induced bistability of turtle motoneurones caused by a nifedipine-sensitive calcium plateau potential.

Abstract: 1. The effect of serotonin on the firing properties of motoneurones was studied in transverse sections of the adult turtle spinal cord in vitro with intracellular recording techniques. 2. In normal medium, turtle motoneurones adapt from an initial high frequency to a low steady firing during a depolarizing current pulse. In the presence of serotonin (4-100 microM) motoneurones responded with accelerated firing and a frequency jump during a depolarizing current pulse followed by an after-depolarization outlasting the stimulus. From a depolarized holding potential motoneuronal activity was shifted between two stable states by brief depolarizing and hyperpolarizing current pulses. As an expression of this bistable firing behaviour, the frequency-current relation in response to a triangular current injection was counter-clockwise in serotonin while clockwise in normal medium. 3. The delay to onset of the frequency jump was shortened as the amplitude of the activation pulse was increased. From a positive holding potential the after-depolarization exceeded spike threshold and its duration increased with an increase in steady bias current. The effect of serotonin on turtle motoneurones could be blocked by methysergide (10 microM). 4. When action potentials were depressed by tetrodotoxin, a voltage-dependent, non-inactivating plateau potential, intrinsic to the motoneurone, was revealed. Activation of this voltage plateau provides the motoneurones with two stable states of firing. The apparent input resistance was 2-4-fold lower during the plateau than at rest. 5. The serotonin-induced plateau potential was Ca2+-dependent and was blocked when Ca2+ was replaced by either Co2+ (3 mM) or Mn2+ (3 mM). 6. The Ca2+ plateau was blocked by nifedipine (1-15 microM). 7. Serotonin reduced the slow after-hyperpolarization following action potentials. The change in balance between inward and outward currents seems to be sufficient to reveal the plateau response. 8. Although a small plateau response was induced by Bay K 8644 (1-15 microM), this L-channel agonist could not reproduce the pronounced effect of serotonin. 9. It is concluded that serotonin induces a Ca2+-dependent and nifedipine-sensitive plateau potential in turtle motoneurones primarily by reducing a K+-current responsible for the slow after-hyperpolarization.

Holocene--late pleistocene climatic ice core records from qinghai-tibetan plateau.

Abstract: Three ice cores to bedrock from the Dunde ice cap on the north-central Qinghai-Tibetan Plateau of China provide a detailed record of Holocene and Wisconsin-Wurm late glacial stage (LGS) climate changes in the subtropics. The records reveal that LGS conditions were apparently colder, wetter, and dustier than Holocene conditions. The LGS part of the cores is characterized by more negative δ 18 O ratios, increased dust content, decreased soluble aerosol concentrations, and reduced ice crystal sizes than the Holocene part. These changes occurred rapidly ∼10,000 years ago. In addition, the last 60 years were apparently one of the warmest periods in the entire record, equalling levels of the Holocene maximum between 6000 and 8000 years ago.

Determination of Brain Interstitial Concentrations by Microdialysis

Abstract: Microdialysis is an extensively used technique for the study of solutes in brain interstitial space. The method is based on collection of substances by diffusion across a dialysis membrane positioned in the brain. The outflow concentration reflects the interstitial concentration of the substance of interest, but the relationship between these two entities is at present unclear. So far, most evaluations have been based solely on calibrations in saline. This procedure is misleading, because the ease by which molecules in saline diffuse into the probe is different from that of tissue. We describe here a mathematical analysis of mass transport into the dialysis probe in tissue based on diffusion equations in complex media. The main finding is that diffusion characteristics of a given substance have to be included in the formula. These include the tortuosity factor (λ) and the extracellular volume fraction (α). We have substantiated this by studies in a welldefined complex medium (red blood cell suspensions) as well as in brain. We conclude that the traditional calculation procedure results in interstitial concentrations that are too low by a factor of λ2/α for a given compound. (Less)

Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics.

Abstract: To develop a reliable experimental model of vascular headache, we studied the dose-response relationship between headache and i.v. nitroglycerin (NTG) in 10 healthy subjects. NTG was infused intravenously over periods of 10 min separated by wash-out periods. Doses of 0.25, 0.50, 1.00 and 2.00 micrograms/kg/min were applied successively with one placebo infusion and wash-out period inserted randomly and double blindly. The subjects scored their headache intensity on a scale 0-10. After 1-8 weeks a retest was performed. Nine subjects developed headache already at 0.25 microgram/kg/min, whereas one had no headache at any dose. Headache severity did not increase with doses above 0.5 microgram/kg/min. This ceiling effect was reproducible. The headache was moderate, usually throbbing, bifrontal and not associated with other migrainous features. It reached maximum within 2.5-5.5 min (medians) at various doses and declined rapidly after NTG discontinuation. Wash-out periods of 10-20 min were sufficient. The reproducibility of headache intensity and character was satisfactory in the retest experiment. There were no unpleasant side effects and no visible flushing. Thus blindness was maintained. I.v. NTG is suitable as an experimental headache model. A constant infusion of 0.5 microgram/kg/min will be suitable for studies of arterial diameter, pulsations, blood flow, etc. Comparative studies of sensitivity should use the present infusion schedule but with the two highest doses substituted by 0.06 and 0.125 microgram/kg/min.

Effect of exercise on insulin action in human skeletal muscle

Abstract: The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2 consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp even though indirect estimates indicated net glycogen synthesis. In contrast, in exercised muscle estimated and biopsy-verified increases in muscle glycogen concentration agreed. Local contraction-induced increases in insulin sensitivity and responsiveness play an important role in postexercise recovery of human skeletal muscle.

Estimating the Doppler centroid of SAR data

Abstract: After reviewing frequency-domain techniques for estimating the Doppler centroid of synthetic-aperture radar (SAR) data, the author describes a time-domain method and highlights its advantages. In particular, a nonlinear time-domain algorithm called the sign-Doppler estimator (SDE) is shown to have attractive properties. An evaluation based on an existing SEASAT processor is reported. The time-domain algorithms are shown to be extremely efficient with respect to requirements on calculations and memory, and hence they are well suited to real-time systems where the Doppler estimation is based on raw SAR data. For offline processors where the Doppler estimation is performed on processed data, which removes the problem of partial coverage of bright targets, the Delta E estimator and the CDE (correlation Doppler estimator) algorithm give similar performance. However, for nonhomogeneous scenes it is found that the nonlinear SDE algorithm, which estimates the Doppler-shift on the basis of data signs alone, gives superior performance. >

Methodological implications of the post activation depression of the soleus H-reflex in man.

Abstract: A long lasting inhibition (> 8 s) of the soleus Hoffmann reflex (H-reflex) was evoked by a preceding soleus H-reflex, by a brief voluntary ankle flexor or extensor muscle contraction or by a tap applied to the Achilles tendon. The time course of this long lasting inhibition was similar in all these cases, suggesting that the same spinal mechanism is involved. Furthermore, it was shown that the post-activation depression may interfere with the determination of inhibitory or facilitatory effects on the H-reflex. It is stressed that when the onset of inhibitory or facilitatory effects on the soleus H-reflex is to be determined in relation to start of an ankle movement, either very long stimulus intervals (> 8 s) must be used, or the onset must be determined in relation to a reference value of the soleus H-reflex, which may be influenced by the long lasting inhibitory effect, but not yet by the succeeding muscle contraction.

Cardiovascular diseases and the work environment. A critical review of the epidemiologic literature on nonchemical factors.

Abstract: This is the first of two articles reviewing the epidemiologic research on cardiovascular diseases (CVD) and the work environment. It deals with a number of nonchemical factors, ie, physical inactivity at work, stressors at work, shift work, noise, cold, heat, and electromagnetic fields and waves. First the methodological quality of each of the empirical studies is assessed on the basis of epidemiologic criteria. Then the research literature on each of the aforementioned factors of the work environment is evaluated. It is concluded that the hypothesis of a causal relationship between physical inactivity at work and risk of CVD is substantially supported by the literature. As regards work stressors and shift work, several good studies have been published during the last 10 years strongly suggesting a causal relationship. Other studies have shown a relationship between noise and elevated blood pressure, but the quality of this literature is low. Heat and cold appear to have an acute effect on the incidence of CVD, but the possible chronic effect has seldom been investigated. Concerning electromagnetic fields and waves, it is concluded that more research is needed. The study of CVD and work ought to play a bigger role in research in the fields of occupational medicine and cardiovascular epidemiology in the future.

Measurements of human pressure-pain thresholds on fingers and toes.

Abstract: Pressure-pain thresholds (PPT) were measured on fingers and toes with a hand-held electronic pressure algometer in 15 males and 15 females. The pressure algometer offered easy control of pressure application rate. The intra-individual coefficient of variation, based on repeated PPT measurements with a 1 week interval was 14%. The inter-individual coefficient of variation was 28% for females and 33% for males. In the course of 10 consecutive PPT measurements with short intervals (10 and 20 sec), no significant change in PPT was observed. PPT was found to be 50% higher in males than in females (P less than 0.0001). Slightly but significantly higher PPT values were found on the dominant compared to the non-dominant side (P less than 0.005).

Partial discharges in ellipsoidal and spheroidal voids

Abstract: Transients associated with partial discharges in voids can be described in terms of the charges induced on the terminal electrodes of the system. The relationship between the induced charge and the properties which are usually measured is discussed. The method is illustrated by applying it to a spheroidal void located in a simple disk-type spacer. >

Ischemic Damage in Hippocampal CA1 is Dependent on Glutamate Release and Intact Innervation from CA3

Abstract: Summary: The removal of glutamatergic afferents to CAl by destruction of the CA3 region is known to protect CA I pyramidal cells against 10 min of transient global isch­ emia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CAl hippocampal tissue. In in­ tact CAl hippocampal tissue, glutamate increased sixfold during ischemia; in the CA3-lesioned CAl region, how­ ever, glutamate only increased 1.4-fold during ischemia. To assess the neurotoxic potential of the ischemia­ induced release of glutamate, we injected the same con­ centration of glutamate into the CAl region as is released during ischemia in normal, CA3-lesioned, and ischemic

The Appearance of Matter Fields from Quantum Fluctuations of 2D Gravity

Abstract: It is established that various critical regimes may occur for a model of two-dimensional pure quantum gravity. These regimes correspond to the presence of effective fields with scaling dimensions Δk=−γstr·k/2, k=1, 2, 3 ..., where γstr=−1/m, m=2, 3, 4 ... is the critical exponent of “string susceptibility” (with respect to the cosmological constant). This behaviour is typical for unitary conformal fields with the central charge c=1−6/m(m+1) in the presence of 2D-quantum gravity. We use the framework of loop equations for the invariant boundary functional, which are exactly solvable in this case.

Spinal mechanisms in man contributing to reciprocal inhibition during voluntary dorsiflexion of the foot.

Abstract: 1 The inhibition of the soleus Hoffmann reflex (H reflex) during voluntary dorsiflexion of the foot--henceforth referred to as ‘natural’ reciprocal inhibition--was found to be initiated 50 ms before the onset of the EMG activity in the tibialis anterior muscle and to increase gradually during a ramp-and-hold dorsiflexion There was a positive correlation between strength of tonic dorsiflexion and amount of ‘natural’ reciprocal inhibition 2 The change of activity in the disynaptic and a long-latency group Ia inhibitory pathway and the change in presynaptic inhibition of the Ia fibres mediating the soleus H reflex were tested separately during ramp-and-hold dorsiflexion as well as during tonic dorsiflexion of the foot, and the results were compared with the development of the ‘natural’ reciprocal inhibition of the unconditioned soleus H reflex 3 The disynaptic group I inhibition of soleus motoneurones was increased, as compared to rest, during the dynamic phase of a ramp-and-hold dorsiflexion movement, but the inhibition generally did not increase during tonic dorsiflexion of the foot 4 The long-latency group I inhibition was seen only during dorsiflexion of the foot It appeared around 50 ms before tibial anterior EMG activity and there was a positive correlation between strength of tonic dorsiflexion and amount of this long-latency inhibition 5 Presynaptic inhibition of Ia afferents terminating on soleus motoneurones was estimated by an indirect method The increase of presynaptic inhibition started soon after the onset of the ramp-and-hold dorsiflexion, and gradually became more pronounced during the ramp phase The amount of presynaptic inhibition was positively correlated with strength of tonic dorsiflexion 6 It is concluded that all investigated mechanisms may contribute to the ‘natural’ reciprocal inhibition and it seems that the different pathways are used differentially during different types of movement

Effects of partial neuromuscular blockade on sympathetic nerve responses to static exercise in humans.

Abstract: We used intraneural recordings of sympathetic nerve activity in conscious humans to determine if central command increases sympathetic discharge to resting skeletal muscle during static exercise. In nine healthy subjects, we measured arterial pressure, heart rate, and muscle sympathetic nerve activity with microelectrodes in the peroneal nerve of the resting leg during 1) static handgrip at 15% and 30% maximal voluntary contraction and 2) attempted handgrip during partial neuromuscular blockade produced by systemic administration of tubocurarine chloride (0.075 mg/kg i.v.). During curare, subjects reported that they used near-maximal motor effort to attempt a sustained handgrip contraction, but they generated almost no force. Without sustained contraction, the intent to exercise alone, that is, central command, caused statistically significant (p less than 0.05) increases in muscle sympathetic nerve activity as well as in arterial pressure and heart rate. However, the increases in muscle sympathetic nerve activity (+ 56 +/- 16% over control) and in mean arterial pressure (+ 12 +/- 2 mm Hg) during attempted handgrip were much smaller (p less than 0.05) than the sympathetic nerve response (+ 217 +/- 37% over control) and pressor response (+ 25 +/- 3 mm Hg) during an actual static handgrip at 30% maximal voluntary contraction. In contrast, heart rate increased as much during the attempted contraction (+ 18 +/- 2 beats/min) as during the actual contraction at 30% maximal voluntary contraction (+ 16 +/- 4 beats/min). In 11 additional subjects, the heart rate responses during curare were greatly attenuated (p less than 0.05) by atropine but were not significantly affected by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

The Charm of Medicines: Metaphors and Metonyms

Abstract: The ready availability and extreme popularity of Western pharmaceuticals in developing countries poses important general issues for medical anthropology. In attempting to explain why medicines are so attractive in so many different cultures, this article suggests that they facilitate particular social and symbolic processes. The key to their charm is their con-creteness; in them healing is objectified. As things, they allow therapy to be disengagedfrom its social entanglements. Medicines are commodities which pass from one context of meaning to another. As substances, they are “good to think with” in both metaphoric and metonymic senses. They enhance the perception of illness as something tangible, and they facilitate communication about experiences that may be difficult to express. In the course of their transaction, they bear with them associations to authoritative professionals and the potency and potential of other cultural contexts of which they once were a part.

The ways of endocytosis.

Abstract: Publisher Summary This chapter focuses on certain aspects of the endocytic pathways of the protein import into cells and the routes they subsequently follow. Transport and sorting of proteins are essential processes for the function and differentiation of eukaryotic cells. The cell utilizes two distinct, specialized organelle systems for the transport and sorting of proteins, one for protein export and the other for protein import. The export system comprises the endoplasmic reticulum (ER) and the Golgi complex. The import system comprises a variety of vesicular structures, the most prominent being endosomes and lysosomes. The role of the various intracellular compartments and of the sorting signals that are needed to deliver specifically the right components to the right compartments, are described in the chapter. The existence of a clathrin-dependent endocytic pathway and some ideas and problems of defining the structural equivalent of this pathway are discussed. The clathrinin-dependent endocytic pathway is used to inhibit the coated-pit pathway. Endocytosis from coated pits can also be inhibited by acidification of the cytosol.

Mix - a self-applicable partial evaluator for experiments in compiler generation

Abstract: The program transformation principle called partial evaluation has interesting applications in compilation and compiler generation. Self-applicable partial evaluators may be used for transforming interpreters into corresponding compilers and even for the generation of compiler generators. This is useful because interpreters are significantly easier to write than compilers, but run much slower than compiled code. A major difficulty in writing compilers (and compiler generators) is the thinking in terms of distinct binding times: run time and compile time (and compiler generation time). The paper gives an introduction to partial evaluation and describes a fully automatic though experimental partial evaluator, called mix, able to generate stand-alone compilers as well as a compiler generator. Mix partially evaluates programs written in Mixwell, essentially a first-order subset of statically scoped pure Lisp. For compiler generation purposes it is necessary that the partial evaluator be self-applicable. Even though the potential utility of a self-applicable partial evaluator has been recognized since 1971, a 1984 version of mix appears to be the first successful implementation. The overall structure of mix and the basic ideas behind its way of working are sketched. Finally, some results of using a version of mix are reported.

Influence of personal characteristics, job-related factors and psychosocial factors on the sick building syndrome. Danish Indoor Climate Study Group.

Abstract: The influence of personal characteristics, life-style, job-related factors, and psychosocial work factors on symptoms of the sick building syndrome was investigated in Greater Copenhagen, Denmark. The buildings were not characterized beforehand as "sick" or "healthy." Of the 4369 employees sent a questionnaire, 3507 returned them. Multivariate logistic regression analyses of the multifactorial effects on the prevalence of work-related mucosal irritation and work-related general symptoms among the office workers showed that sex, job category, work functions (handling of carbonless paper, photocopying, work at video display terminals), psychosocial factors of work (dissatisfaction with superiors or colleagues and quantity of work inhibiting job satisfaction) were associated with work-related mucosal irritation and work-related general symptoms, but these factors could not account for the differences between the buildings as to the prevalence of the symptoms. The building factor (i.e., the indoor climate) was strongly associated with the prevalence of the symptoms.

Direct evidence that excitotoxicity in cultured neurons is mediated via N-methyl-D-aspartate (NMDA) as well as non-NMDA receptors.

Abstract: Cultured GABAergic cerebral cortex neurons were exposed to the excitatory amino acid (EAA) L-glutamate, kainate (KA), N-methyl-D-aspartate (NMDA), or RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionate (AMPA). To ensure a constant glutamate concentration in the culture media during the exposure periods, the glutamate uptake inhibitor L-aspartic acid beta-hydroxamate was added at 500 microM to the cultures that were exposed to glutamate. Each of these EAAs was able to induce neurotoxicity. It was not possible to reduce or prevent glutamate-induced cytotoxicity by blocking only one of the glutamate receptor subtypes with either the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoate (APV) or with one of the specific non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). However, if the cultures were exposed simultaneously to glutamate and the antagonists in combination, i.e., APV plus CNQX or APV plus DNQX, the toxicity was completely prevented. Furthermore, CNQX and DNQX were shown to be selective blockers of cytotoxic phenomena induced by non-NMDA glutamate agonists with no effect on NMDA-induced cell death. Likewise, APV prevented NMDA-induced cell death without affecting the KA- or AMPA-induced neurotoxicity. It is concluded that EAA-dependent neurotoxicity is induced by NMDA as well as non-NMDA receptors.

Lipoprotein metabolism influenced by training-induced changes in human skeletal muscle.

Abstract: The influence of training-induced adaptations in skeletal muscle tissue on lipoprotein metabolism was investigated in six healthy men. The knee extensors were studied at rest and during exercise after 8 wk of dynamic exercise training of the knee extensors of one leg, while the other leg served as a control. The trained and nontrained thighs were investigated on different occasions. In the trained knee extensors, muscle (m) lipoprotein lipase activity (LPLA) was 70 +/- 29% higher compared with the nontrained (P less than 0.05), and correlated positively with the capillary density (r = 0.84). At rest there was a markedly higher arteriovenous (A-V) VLDL triacylglycerol (TG) difference over the trained thigh, averaging 55 mumol/liter (range 30-123), than over the nontrained, averaging 30 mumol/liter (4-72). In addition to the higher LPLA and VLDL-TG uptake in the trained thigh, a higher production of HDL cholesterol (C) and HDL2-C was also observed (P less than 0.05). Positive correlations between m-LPLA and A-V differences of VLDL-TG (r = 0.90; P less than 0.05) were observed only in the trained thigh. During exercise with the trained thigh the venous concentration of HDL2-C was invariably higher than the arterial, and after 110 min of exercise a production of 88 mumol/min (54-199) of HDL2-C was revealed. Even though a consistent degradation of VLDL-TG was not found during exercise, the total production of HDL-C across the trained and nontrained thigh, estimated from A-V differences times venous blood flow for the whole exercise period, correlated closely with the total estimated degradation of VLDL-TG (r = 0.91). At the end of 2 h of exercise m-LPLA did not differ from the preexercise value in either the nontrained or the trained muscle. We conclude that changes in the lipoprotein profile associated with endurance training to a large extent are explainable by training-induced adaptations in skeletal muscle tissue.