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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 253 records · Page 14Linked to original sources
PubMed1990

Rapid inhibition of the c-jun proto-oncogene expression in avian oviduct by estrogen.

The c-jun proto-oncogene codes for an important component of the AP-1 transcription factor complex which regulates the expression of many genes. This paper demonstrates that the steady state c-jun mRNA level in the avian oviduct is markedly decreased to 50% of control values within 30 minutes after estrogen injection into the animals. In the avian liver, the level is rapidly increased over 10 fold. Nuclear run-off transcription analysis demonstrates that the decrease in the c-jun mRNA levels in the avian oviduct occurs at least in part at the level of transcription. These changes are reproducible in repeat experiments. This response in the avian oviduct is unique since 1) it is the first demonstration of a steroid effect on c-jun expression in any animal system, 2) the changes in c-jun mRNA occur much more rapidly than most steroid responsive genes, and 3) it is the rare demonstration of an estrogen inhibition of the expression of a gene. A role for the c-jun proto-oncogene as an early regulatory gene in the cascade model for steroid action is proposed.

Animals↗
PubMed1990

The clinical evaluation of cobalamin deficiency by determination of methylmalonic acid in serum or urine is not invalidated by the presence of heterozygous methylmalonic-acidaemia.

It is well established that accumulation of methylmalonic acid may provide an early clue to the existence of tissue cobalamin (vitamin B12) deficiency. To verify whether methylmalonic acid accumulates in adult heterozygotes for inherited methylmalonic-acidaemia and thereby gives "false" positive test results for cobalamin deficiency, we measured the concentration of methylmalonic acid in serum and its urinary excretion in six patients of three children with severe methylmalonic-acidaemia. We found levels of methylmalonic acid similar to those in normal subjects. In serum, the concentrations of methylmalonic acid ranged from 0.12 to 0.39 mumol/l (reference range: 0.05-0.44 mumol/l). In urine, the values ranged from 1.18 to 2.48 mmol per mol of creatinine (reference range: 0.58-3.56). We conclude that the 2% of carriers of inherited methylmalonic-acidaemia in the general population do not invalidate the usefulness of measurement of methylmalonic acid in serum or urine for the clinical evaluation of cobalamin deficiency.

Adult↗
PubMed1990

Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates.

We have compared the time course of the behavioral manifestations of opiate withdrawal to the in vivo activity of locus coeruleus (LC) neurons and to increases in the levels of G-proteins, adenylate cyclase, and cAMP-dependent protein kinase known to occur in the LC in opiate-dependent animals. Rats were given morphine by daily subcutaneous implantation of morphine pellets for 5 d. On the sixth day, morphine withdrawal was induced by subcutaneous administration of naltrexone, an opiate receptor antagonist, with additional doses given 6 and 24 hr later, conditions that resulted in sustained, maximal levels of withdrawal over the duration of the experiment. We found a striking parallel between the time courses of the behavioral signs and the increased activity of LC neurons during withdrawal, both of which appeared to follow 2 phases. There was an early, rapid phase, during which withdrawal signs and increased LC activity became most pronounced within 15-30 min after naltrexone administration, and then recovered rapidly by over 50% within 4 hr of withdrawal. Subsequently, there was a slower phase, during which the persisting withdrawal signs and elevated LC activity remained roughly constant from 4 to 24 hr and did not recover completely until after 72 hr of continuous withdrawal. Adenylate cyclase and cAMP-dependent protein kinase activities in isolated LC subcellular fractions, both elevated in dependent animals, recovered to control levels after 6 hr of withdrawal, in parallel with the rapid phase of withdrawal. Levels of G1 and Go, also elevated in dependent animals, remained only slightly elevated at 6 hr and returned to normal by 24 hr. Taken together, these data suggest that increased neuronal activity in the LC is associated temporally with the behavioral morphine withdrawal syndrome and that increased levels of G-proteins and an up-regulated cAMP system may contribute to the early withdrawal activation of these neurons.

Adenylyl Cyclases↗
PubMed1990

Modulation of adrenal chromaffin cell intracellular calcium by angiotensin, bradykinin and endothelin.

Studies were undertaken to compare and contrast the effects of the vasoactive peptides, angiotensins II and III, bradykinin and endothelin, on mobilization of intracellular calcium in isolated, cultured bovine adrenal medullary (chromaffin) cells. Calcium mobilization was studied using the Fura-2 technique. The potency for elevating intracellular calcium, compared on a molar basis, was bradykinin greater than angiotensin III greater than angiotensin II much greater than endothelin. When nicotine and angiotensin II were added together, a synergism was evident with prolonged elevation of intracellular calcium. However, concomitant addition of angiotensin II and endothelin was barely additive. Yet, combined addition of endothelin and depolarizing potassium chloride yielded a very marked synergism in calcium mobilization. We conclude that the multiplicity of vasoactive peptide receptors on chromaffin cells exert interactive modulation on calcium mobilization in these cells and this property may have functional significance.

Adrenal Medulla↗
PubMed1990

Methylmalonic acid concentrations in serum of normal subjects: biological variability and effect of oral L-isoleucine loads before and after intramuscular administration of cobalamin.

The clinical value of measuring concentrations of methylmalonic acid in serum (S-MMA) as an aid in the diagnosis of cobalamin deficiency has recently aroused interest. In 58 healthy subjects, ages 40-68 years, we found a 0.95 reference interval of 0.05-0.37 mumol/L (mean 0.21, SD 0.094). In 33 of the subjects, who were studied further, day-to-day variation (SD) was 0.031 mumol/L. Intake of food had no effect. Weekly and three-monthly intra-individual variations were both 0.038 mumol/L. In all seven subjects with S-MMA greater than 0.30 mumol/L, the concentrations declined significantly after intramuscular administration of cobalamin. No significant difference was found between mean serum cobalamin concentrations in these seven and in the remaining subjects. We have also established the normal response of S-MMA to standardized oral loading of L-isoleucine: 100 mmol caused a significant average S-MMA increase of 0.072 mumol/L before cobalamin administration vs 0.013 mumol/L after cobalamin, without significant relation to initial S-MMA values. Our results provide a necessary background for interpretation of S-MMA measurements in clinical studies.

Administration, Oral↗
PubMed1989

Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis.

Single unit activity was recorded in the locus coeruleus (LC) of anesthetized, morphine-dependent rats during naltrexone-precipitated withdrawal. As has been reported previously, LC neurons displayed a strong withdrawal-induced activation of firing rate. Radio-frequency lesions of the nucleus paragigantocellularis (PGi), a major LC afferent, greatly attenuated withdrawal-induced activation of neurons in the LC ipsilateral but not contralateral to the PGi lesion. Lesions of the prepositus hypoglossi, another major LC afferent, did not prevent the withdrawal-induced activation of LC neurons. Kynurenic acid, a non-selective excitatory amino acid antagonist known to block PGi-induced excitations of LC neurons, also blocked the withdrawal-induced activation of LC neurons. These studies indicate that withdrawal-induced activation of the LC in opiate-dependent rats is mediated at least in part by afferents from the PGi which utilize an excitatory amino acid transmitter.

Action Potentials↗
PubMed1989

Depolarization potentiates endothelin-induced effects on cytosolic calcium in bovine adrenal chromaffin cells.

The effects of endothelin on intracellular calcium concentrations ([Ca2+i]) in primary cultures of bovine adrenal chromaffin cells (BAM) were measured using Fura 2. Endothelin had minimal effects on [Ca2+i] over a broad dose range (1 nM to 1 microM). However, in conjunction with K+ depolarization there was a synergistic increase in [Ca2+i]. This effect was dependent on extracellular calcium as was the response to KCl alone. A partial synergistic effect was evident with endothelin and nicotinic stimulation. The effects of endothelin and angiotensin II on [Ca2+i] are only additive. Blockade of voltage sensitive calcium channels failed to alter the synergistic effects. Our results indicate that endothelin influences BAM calcium mobilization through sites regulated by membrane depolarization but differing from traditional voltage sensitive calcium channels.

Adrenal Medulla↗
PubMed1989

[Bronchial asthma caused by isocyanate in the internal/external environment].

Di-isocyanates have resulted in sensitizing and bronchial asthma in 4-5% of exposed workers in industry. A case of bronchial asthma is described in which the primary sensitization occurred during the period 1968-1970 as a result of work in a factory producing polyurethane plastic foam. The patient sought other employment on account of severe asthmatic symptoms and was, thereafter, symptom-free for 15 years. He was then engaged in a factory in the neighbourhood of the plastic foam factory and the asthmatic symptoms recurred on account of exposure via the external environment. The influences of various public authorities on handling of this case are described.

Asthma↗
PubMed1989

[Simultaneous transplantation of the pancreas and kidney in terminal diabetic nephropathies].

Transplantation of the pancreas in late stages of type I diabetes has been performed increasingly frequently during recent years. By improved surgical techniques and immunsuppressive therapy including cyclosporin A, the 1-year graft function has increased to 60-70% and the patient survival to 85-95% in the institutions with greatest experience. These results are so good, that they nearly reach those from kidney transplantation. Most of the pancreas transplantations have been performed simultaneously with kidney transplantation in patients with end stage diabetic uremia. The results should therefore be evaluated according to these circumstances. In a few institutions transplantation of the pancreas is now performed in patients with persistent proteinuria and proliferative retinopathy in an attempt to avoid development of severe diabetic complications. The first pancreas transplantation in Denmark was performed Januar 31 st 1987, and since then, 17 further transplantations have been performed. All patients had severe diabetic nephropathy and received simultaneous kidney transplantation. According to the Danish heart death criteria the organs were perfused and cooled during the donor operation to keep the warm ischemia as brief as possible. The pancreatic vessels are anastomosed to the iliac vessels. In one group of patients the exocrine pancreatic function was preserved by anastomosis to the jejunum, and in another group of patients the exocrine function was abolished by injection of latex into the pancreatic duct system. The patients receive immunosuppression therapy with methylprednisolone, azatioprine and ciclosporin A and anti-coagulation therapy.

Denmark↗
PubMed1989

Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices.

In general, it has been difficult to preserve electrophysiologically viable motoneurons in brain slices from adult mammals. The present study describes a new method for obtaining viable motoneurons in the facial nucleus of adult rat brain slices. The essence of the method was to use a modified artificial cerebrospinal fluid (ACSF) in which NaCl was replaced initially by sucrose; the modified ACSF was used during 1) preparation and 2) a 1 hr recovery period. The rationale for the modification is discussed in terms of the proposed acute neurotoxic effects of passive chloride entry and subsequent cell swelling and lysis. The actual recordings were made only after switching back to normal ACSF. Use of this method yielded large numbers of viable motoneurons that were suitable for intracellular recording; no motoneurons survived when normal ACSF (i.e., with NaCl) was used during slice preparation. A survey of some electrophysiological and pharmacological properties of facial motoneurons in this preparation, by means of current-clamp and voltage-clamp recording, revealed close similarities to the properties of adult motoneurons previously observed in vivo (e.g., time-dependent inward rectification, apamin-sensitive afterhyperpolarization, and serotonin-induced slow depolarization).

Action Potentials↗
PubMed1989

An investigation of the effect of regional variation in the treatment of hypertension.

Over a period both a monetary and physical measure of antihypertensive drug consumption has increased in Denmark, but the consumption has varied considerably between counties in any given year. Concurrently, SMR for myocardial infarctions and cerebrovascular diseases due to hypertension has declined. The relation between intensity of treatment and outcome in terms of reduced loss of life time or healthy time is analyzed at an aggregate level within a health economic framework. The relation is analyzed by using a pooled time series cross section regression analysis. Two models, a covariance and an error component model are used. Within the range of observed drug consumption, loss of life years and loss of good health show a tendency towards negative regression on consumption of drugs when controlled for relevant variables such as occupational structure, degree of urbanization, and hardness of the drinking water.

Antihypertensive Agents↗
PubMed1989

Monitoring of pancreas-graft perfusion by radionuclide and digital subtraction angiography.

The vascularity of a kidney transplant can be evaluated by intravenous radionuclide angiography. A normal functioning transplant should have an isotope histogram with a well-defined peak. Accordingly, a transplanted pancreas may be evaluated in the same way. By intravenous digital subtraction angiography and small amounts of contrast medium, arterial and venous structures can be visualized without catheterization of the arterial system. Five patients had combined kidney and pancreas transplantation. Intravenous angiography with 99mTc-pertechnetate was performed three times a week for the first 5 postoperative wk. Digital subtraction angiography with an intravenous bolus of 80 ml of a low-osmolar nonionic contrast medium (iopamidol) was performed late in the postoperative course or when severe impairment of pancreas-graft perfusion was discovered by radionuclide angiography. One patient had two episodes and three patients one episode of rejection of both kidney and pancreas. Impairment of the pancreas-graft perfusion always preceded or was associated with deterioration of the graft function. In all patients, digital subtraction angiography demonstrated the graft vessels in sufficient detail. No thrombotic complications were observed. We conclude that these two methods can be used for monitoring the kidney and pancreas-graft perfusion. The methods may be of great value, especially in the early postoperative period, when problems with organ function are frequent and early intervention is essential.

Contrast Media↗
PubMed1989

Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.

Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients.

Adult↗
PubMed1989

Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.

Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005).

Adult↗