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Biomedical subjects

P Nilsson

Publications and source records attributed to P Nilsson.

At least 19 recordsLinked to original sources
PubMed1992

DNA binding of histone H1 is modulated by nucleotides.

Histone H1 acts as a general repressor of transcription in eukaryotes by organizing nucleosomes into inaccessible condensed forms of chromatin. The capability of H1 to bind to DNA with some sequence specificity is likely to be critical in the control of these processes. We show here that ATP and several other nucleotides, including non-hydrolyzable derivatives, can inhibit DNA binding of H1. The results also show that ATP differentially affects binding of H1 to DNA in a fashion enhancing nucleotide sequence specificity of the binding. The study suggests a novel mechanism of modulation of H1 activity that has important implications for the role of H1 as a transcriptional regulator.

Amino Acid Sequence↗
PubMed1992

Prevalence of abdominal aortic aneurysm in the offspring of patients dying from aneurysm rupture.

The prevalence of abdominal aortic aneurysm (AAA) is high in the brothers of patients with aneurysm. A genetic component in the development of AAA has, therefore, been postulated. In this study the offspring of patients who had died from AAA rupture were invited to undergo ultrasonography of the abdominal aorta. The attendance rate was 69 per cent. Thirty-nine sons of median age 60 (range 45-75) years and 23 daughters of median age 62 (range 42-80) years were examined. Abdominal aortic dilatation was found in eight men and one woman. The presence of aortic dilatation in these nine cases was not related to age, hypertension, smoking or symptoms of occlusive arterial disease. It is concluded that the sons of those who have died from ruptured AAA constitute a high-risk group for the development of this condition and should be considered for further screening.

Aged↗
PubMed1992

Cholelithiasis during the first year of life: case reports and literature review.

Five cases are reported of children with gallstones diagnosed by ultrasound during their first 7 months of life. Of the four with symptomatic gallstones, one subsequently developed vitamin K deficiency syndrome with profuse bleedings. The children, who belonged to a defined population, were all diagnosed within an 18-month span, suggesting the frequency of early gallstone formation to be higher than formerly supposed. One child had haemolytic anaemia, but none of the conventional risk factors for stone formation was present in the other four cases.

Child, Preschool↗
PubMed1992

Normal tissue reactions in mice after combined treatment with metoclopramide and ionizing radiation.

We have previously shown that metoclopramide potentiates the effect of ionizing radiation and cisplatin treatment of human squamous cell carcinomas from the head and neck region xenografted to nude mice. In the present tumor study, the dose scheduling of metoclopramide in combination with radiation was evaluated, and metoclopramide was shown to be most effective in potentiating the cytotoxic effect of radiation when administered one hour before radiation. The effect of radiation in combination with metoclopramide on normal tissue was also studied in two well-established models. Acute skin reactions to radiation exposure were studied in 129-type mice, and metoclopramide did not enhance the acute skin reaction in this in vivo model. Survival after whole body irradiation was studied in heterozygote Balb/c nu/+ mice as a measure of bone marrow toxicity. Metoclopramide was not found to affect the LD50/30 in this in vivo model. The absence of potentiation of radiation damage to normal tissue in these animal studies, makes metoclopramide an interesting possibility for future clinical evaluation.

Animals↗
PubMed1991

Differential decay of a polycistronic Escherichia coli transcript is initiated by RNaseE-dependent endonucleolytic processing.

Differential expression of the genes expressing Pap pili in Escherichia coli was suggested to involve mRNAs with different stabilities. As the result of a post-transcriptional processing event, a papA gene-specific mRNA product (mRNA-A) accumulates in large excess relative to the primary mRNA-BA transcript. Our results show that the processed product, mRNA-A, is a translationally active molecule and that it is generated from the mRNA-BA precursor by an RNaseE-dependent mechanism. The processing did not occur under non-permissive conditions in an E. coli rne mutant strain with a temperature-sensitive RNaseE. The endonuclease RNaseE was previously described as being chiefly involved in the processing of the 9S precursor of 5S rRNA. A comparison of nucleotide sequences of mRNA-BA and three other RNAs processed by RNAseE revealed a conserved motif around the cleavage sites. Mutations abolishing the activity of either of two other endoribonucleases, RNaseIII and RNaseP, did not affect the pap mRNA processing event. However, a conditional mutation in the ams locus, causing altered stability of bulk mRNA in E. coli, led to reduced pap mRNA processing in a manner similar to the effect caused by RNaseE deficiency. Our findings are consistent with the idea that ams is related/allelic to rne. Absence of the processing event in the RNaseE mutant (rne-3071) strain led to a four-fold stabilization of the mRNA-BA primary transcript. We conclude that the RNaseE-dependent processing event is the rate-limiting step in the decay of the papB-coding part of the primary transcript and in the production of the stable mRNA-A product.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Outer Membrane Proteins↗
PubMed1991

The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats.

Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from the circulation with a T1/2 alpha of 2.9 min and a T1/2 beta of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated that 125I-rIL-1 beta was localized to the proximal tubules in the kidney and to the hepatocytes in the liver. Furthermore, grains were localized to the islets of Langerhans in the pancreas. Tracer-bound proteins corresponding to intact 125I-rIL-1 beta were found in the circulation after i.v., intraperitoneal (i.p.) and subcutaneous (s.c.) injections, as demonstrated by high performance size exclusion chromatography, trichloracetic acid precipitation and SDS-PAGE until 5 h after tracer injection. Pre-treatment with 'cold' rIL-1 beta enhanced degradation of a subsequent injection of tracer. The route of administration was of importance for the biological effects of rIL-1 beta, as demonstrated by a reduced food intake, increased rectal temperature and blood glucose after s.c. injection of rIL-1 beta compared with i.p. The present demonstration of intact rIL-1 beta in the circulation and the islets of Langerhans supports the hypothesis that systemic IL-1 beta may be involved in the initial beta-cell destruction leading to IDDM in humans.

Animals↗
PubMed1991

Lower-limb vasospasm and renal failure during postoperative thromboprophylaxis. Case report.

In a 73-year-old woman with trimalleolar fracture, secondary acute ischemia of the limb and renal failure developed in association with heparin-dihydroergotamine thromboprophylaxis. Earlier cases of thromboprophylaxis-related angiospasm are briefly reviewed. The condition is infrequent, but trauma of extremities and shock are risk factors. Renal failure is rare.

Acute Kidney Injury↗
PubMed1990

Trauma-induced increase of extracellular ascorbate in rat cerebral cortex.

Extracellular (EC) ascorbate concentrations were measured in microdialysates from the cerebral cortex in rats subjected to cortical compression-contusion trauma. The trauma induced a transient, dramatic increase in EC ascorbate compared to the basal level before the insult and compared to control animals. The data support the presence of a releasable intracellular pool of ascorbate in the neocortex. The possibility that ascorbate may influence traumatic brain damage by its proposed neuromodulatory property and/or by its ability to induce lipid peroxidation is considered.

Animals↗
PubMed1990

Transcriptional silencing and thermoregulation of gene expression in Escherichia coli.

Expression of specific adhesive properties by bacteria in general seems to be regulated to fit the environmental conditions. An example is the transcriptional regulation of digalactoside-specific binding by uropathogenic strains of Escherichia coli. The fimbrial structures (pili) on the bacterial surface carry the adhesin and are present during growth at 37 degrees C but are not produced by cells at lower temperatures, such as 25 degrees C. Thermoregulation of expression is due to temperature-dependent transcription of a regulatory cistron in the pilus-adhesin gene cluster. We have now identified and characterized a new regulatory locus (drdX) and show that a histone-like bacterial protein has an important role in this novel example of thermoregulation of transcription.

Adhesins, Bacterial↗
PubMed1990

Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats.

The aim of this study was to measure extracellular chemical changes in the cerebral cortex in response to compression contusion trauma in rats. Energy-related metabolites (i.e., lactate, pyruvate, adenosine, inosine, and hypoxanthine) and amino acids were harvested from the extracellular fluid (ECF) using microdialysis and analyzed by high-performance liquid chromatography. The measurements were performed in cortical tissue, where neuronal injury occurs in this model. The severity of the trauma was varied by using different depths of impact: mild trauma, 1.5 mm; severe trauma, 2.5 mm. The trauma induced a dramatic increase in the ECF levels of energy-related metabolites that was conditioned by the severity of the insult. The ECF level of taurine, glutamate, aspartate, and gamma-aminobutyric acid (GABA) also rose markedly, while other amino acids did not change significantly. The results suggest that the trauma induced a transient, profound focal disturbance of energy metabolism in the cortical tissue, probably as a result of mechanically induced disruption of ion homeostasis and reduced blood flow in combination. The data support the potential role of glutamate and aspartate as mediators of traumatic brain injury. However, the concomitantly released adenosine, GABA, and taurine may be protective and ameliorate excitotoxicity. In analogy with the reported cumulative damaging effects of repeated ischemic insults, the observed ECF changes may help explain the vulnerability of traumatized brain tissue to secondary ischemia.

Adenosine↗
PubMed1990

A generalized formulation of the 'incomplete-repair' model for cell survival and tissue response to fractionated low dose-rate irradiation.

A generalized equation for cell survival or tissue effects after fractionated low dose-rate irradiations, when there is incomplete repair between fractions and significant repair during fractions, is derived in terms of the h- and g-functions of the 'incomplete-repair' (IR) model. This model was developed originally from the concept of 'dose equivalent of incomplete repair', assuming that the repair of radiation damage is an exponential function of time and that the cell survival curve can be described adequately by the linear quadratic (LQ) formalism. The generalized incomplete-repair equation is shown to be equivalent to an expression derived by Dale et al. (1988) for analysis of tissue effects of fractionated irradiations at varying dose rates. The model is critically dependent on alpha/beta, repair half-time, treatment time and interfraction interval, and should therefore be regarded primarily as a tool for the analysis of fractionation and dose-rate effects in carefully designed radiobiological experiments, although it should also be useful in exploring, in a general way, the feasibility of clinical treatment protocols using fractionated low dose-rate treatments.

Cell Survival↗
PubMed1990

Hyperinsulinaemia and other metabolic disturbances in well-controlled hypertensive men and women: an epidemiological study of the Dalby population.

Hypertensive subjects who have received no treatment have been found to be hyperinsulinaemic in previous studies using different populations. The present study was carried out to further examine the metabolic disturbances in carefully treated hypertensive subjects [diastolic blood pressure (DBP) less than 90 mmHg] of both sexes from the Dalby population. Three hundred and ten subjects who had been hypertensive for more than 5 years [DBP 88.1 +/- 0.5 (mean +/- s.e.m.)] were compared with 288 normotensive controls, matched for sex and age and chosen from the same population. After an overnight fast and with no medication for 24 h, an oral glucose tolerance test was carried out. P-insulin and P-C-peptide were analysed and insulin sum (P-insulin at start + after 2 h of oral glucose tolerance test) and C-peptide sum were calculated. Insulin and C-peptide sums were higher (P less than 0.001) in the hypertensive than in the normotensive subjects; 0.69 +/- 0.03, 3.36 +/- 0.08 and 0.41 +/- 0.02, 2.74 +/- 0.06, respectively. The diagnosis of hypertension, not the attained blood pressure level, correlated with insulin and C-peptide sums in multivariate analyses; F-values 20.96 (n = 598; P less than 0.001) and 6.68 (P less than 0.01), respectively. Hypertensive subjects under treatment, using calcium antagonists as monotherapy (n = 21), did not differ in age or body mass index from other hypertensives, but they had lower values for insulin and C-peptide sums; 0.45 +/- 0.05 and 2.63 +/- 0.18. Angiotensin converting enzyme inhibitors were not frequently used for monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1990

High urinary cAMP in hypertensives despite careful drug treatment--an epidemiological study from the Dalby population.

The correlation between serum calcium (S-Ca), plasma parathyroid hormone (P-PTH) and hypertension was determined in a population-based, cross-sectional study of carefully treated hypertensives (n = 391; diastolic blood pressure 90.2 mmHg; 57 years) compared with normotensive controls (n = 328; diastolic blood pressure 82.1 mmHg; 57 years). Levels of urinary cyclic-adenosinemonophosphate (U-cAMP), but not of plasma cAMP (P-cAMP), were higher (P less than 0.001) in hypertensives than in controls. This was the case regardless of the type of drug treatment and the blood pressure level that was reached. U-cAMP correlated with adrenaline in multivariate analyses. S-Ca levels were higher (P less than 0.001) and S-Mg levels were lower (P less than 0.001) in hypertensives than in controls. This was not explained by thiazide treatment. Thus, despite 'adequate' blood pressure reduction, substantial differences in S-Ca, S-Mg and U-cAMP still exist between hypertensives and normotensive controls.

Antihypertensive Agents↗
PubMed1990

Calculation and measurements of absorbed dose in total body irradiation.

A method which is simple, reliable, and rapid to use in clinical routine for basic dose calculation in total body irradiation (TBI) has been tested with 8 MV x-rays. The dosimetry follows, as far as possible, national and international recommendations for conventional radiotherapy. The dose rate at different locations and depths is calculated from the absorbed dose rate at dose maximum for a phantom size of 30 x 30 x 30 cm in the TBI field (Dc), an inverse square law factor (SAD2/SPD2), the tissue-maximum ratio (TMR), an equivalent phantom and patient size correction factor (A), a factor for lack of back-scattering material (B), an off-axis output correction factor (O), and a factor that corrects for off-axis variations in effective photon beam energy and for oblique beam penetration of the patient (R). The collimator opening is constant for all patient sizes. It is shown that TMR, A, B and R can be measured in conventional geometry in ordinary phantoms but at an extended distance, while Dc, O and SAD2/SPD2 must be measured in TBI geometry. Tests in Humanoid phantoms showed an agreement in measured and planned AP/2 doses of 2% or better. If the calculation method is used for lower photon energies or in other TBI geometries it may be necessary to correct for the elliptical shape of the patient and for back-scattered radiation from the walls or floor.

Radiation Dosage↗