[Ischemic treatment of cancer--a break-through?].
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Arteries↗
Biomedical subjects
B Persson
Publications and source records attributed to B Persson.
Renal and hemodynamic effects of isradipine in essential hypertension.
Twenty-three men with essential hypertension participated in a double-blind placebo-controlled study with a crossover design to evaluate the long-term (nine weeks) effects of isradipine on central and renal hemodynamics. Isradipine as monotherapy was titrated from 2.5 to 5 and then to 7.5 mg twice daily. At the end of the crossover periods, cardiac output (dye-dilution) and intraarterial blood pressure were assessed. Compared with placebo, isradipine reduced ambulatory blood pressure from 174/104 to 154/91 (p less than 0.001), whereas the heart rate was unchanged. The reduction of blood pressure was entirely due to a reduction (36 percent; p less than 0.001) of the peripheral resistance. The baroreceptor sensitivity did not change (RR intervals during infusion of phenylephrine) but, with isradipine, the setpoint was shifted to lower blood pressure levels. Renal plasma flow (para-amino hippurate clearance) increased (465 versus 391 ml/minute; p less than 0.05), but glomerular filtration rate ([51Cr]ethylenediaminetetraacetic acid clearance) did not change. Hence, the filtration fraction decreased. With isradipine, there was a post-dose increase in natriuresis (0.45 to 0.34 mmol/minute; p = 0.06). Side effects were mild.
Antihypertensive Agents↗
Human insulin-like growth-factor-binding protein. Low-molecular-mass form: protein sequence and cDNA cloning.
Two different insulin-like growth-factor (IGF)-binding proteins have been found in human blood, one of high molecular mass and dependent on growth hormone for synthesis, the other of low molecular mass and independent of growth hormone. The small IGF-binding protein is abundant in human amniotic fluid. Its amino acid sequence has now been determined by direct analysis of the protein and its proteolytic fragments. Also, by immunoscreening a partial cDNA clone was isolated from a human hepatoma cell line. The mature protein consists of 234 amino acids and is coded for by an mRNA of approximately 1700 nucleotides in length. The primary structure of the protein reveals 18 Cys residues in N-terminal and C-terminal clusters and an Arg-Gly-Asp peptide sequence, common to extracellular proteins binding to receptors of the integrin family. A protein-sequence polymorphism was detected at position Ile/Met-228, indicating possible allelic variation. The 3'-untranslated mRNA sequence has a high A + T content and shows five copies of an ATTTA sequence, which has been shown to be involved in the regulation of the stability of certain mRNAs coding for growth-regulating proteins.
Amino Acid Sequence↗
Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase.
A structural homology between lipoprotein lipase, pancreatic lipase and hepatic lipase is known and indicates that all three lipases are members of a common protein family. Lipoprotein lipase and pancreatic lipase utilize small protein co-factors, apolipoprotein C-II and co-lipase, respectively, but comparisons reveal no homology between the co-factor molecules. Hence, they do not show the same relationship as their target enzymes. Neither do screenings detect any extensive similarities between lipoprotein lipase, serine hydrolases, or apolipoproteins. Scannings against data bank proteins show that a 105-residue segment of lipoprotein lipases exhibits a 35-40% residue identity with a sub-region of Drosophila vitellogenins. One fifth of the conserved amino acid residues (8 of 40) are glycine, a pattern which is typical of distantly related forms of protein families. This supports a true relationship between large segments of Drosophila vitellogenins and lipases. Physiological and functional aspects of the vitellogenin/lipoprotein lipase similarities are given. The region concerned is entirely within the N-terminal domain of lipoprotein lipase and constitutes the segment where the similarity to hepatic and pancreatic lipases is most pronounced. Within this lipase region a 10-residue putative lipid-binding site exists for which further similarities have been found to the otherwise not closely related lingual/gastric lipases, prokaryotic lipases and lecithin-cholesterol acyltransferase. Another segment in lipoprotein lipase, where the heparin-binding site has been mapped, exhibits a correlation between strength of heparin binding and extent of basic residues among members of the lipase family. It further exhibits weak similarities with the 'Zn-finger' DNA-binding segment of steroid hormone receptors and may indicate convergence in a binding interaction. Thus, a functional subdivision of lipoprotein lipase into different segments can be distinguished.
Amino Acid Sequence↗
Primary structure of the hemoglobin beta-chain of rose-ringed parakeet (Psittacula krameri).
The primary structure of Rose-ringed Parakeet hemoglobin beta-chain was established, completing the analysis of this hemoglobin. Comparison with other avian beta-chains show variations smaller than those for the corresponding alpha-chains. There are 11 amino acid exchanges in relationship to the only other characterized psittaciform beta-chain, and a total of 35 positions are affected by differences among all avian beta-chains analyzed (versus 61 for the alpha-chains). At three positions, the Psittacula beta-chain has residues unique to this species. Three alpha 1 beta 1 contacts are modified, by substitutions at positions beta 51, beta 116, and beta 125.
Amino Acid Sequence↗
Blood pressure control and haemodynamic adaptation with the dihydropyridine calcium antagonist isradipine: a controlled study in middle-aged hypertensive men.
Twenty-three middle-aged men (59 +/- 2 years) with sustained, essential hypertension (WHO Stage II) and with diastolic blood pressure exceeding 100 mmHg during a run-in placebo month were included in a trial designed to assess the clinical and haemodynamic effects of isradipine, a novel dihydropyridine calcium antagonist. The study was double-blind with a placebo-controlled crossover design. Isradipine as monotherapy was titrated in three, 3-week periods in doses of 2.5, 5 and 7.5 mg twice daily, or as apparently identical placebo capsules. A 3-week placebo wash-out period separated the two phases of the study. Clinical characteristics were followed during each treatment phase and an invasive haemodynamic examination was performed on the last day of the final active or placebo dose. In the haemodynamic investigation, cardiac output was measured using a dye-dilution technique and blood pressure via a catheter in the brachial artery. Plasma renin activity (PRA) was assessed by radio-immunoassay of generated angiotensin I and arterial noradrenaline concentrations using high-performance liquid chromatography (HPLC). Baroreceptor sensitivity was calculated from R-R intervals of the ECG and beat-to-beat systolic blood pressure during increasing bolus injections of phenylephrine. During optimal therapy with isradipine (7.5 mg twice daily), highly significant decreases in supine systolic (from 174 +/- 4 to 154 +/- 3 mmHg) and diastolic blood pressures (from 104 +/- 2 to 91 +/- 1 mmHg) were observed. Heart rate was unchanged (79 +/- 3 versus 81 +/- 2 beats/min) during chronic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Long-term renal effects of isradipine, a calcium entry blocker, in essential hypertension.
The long-term effects (9 weeks) on renal hemodynamics of the new calcium entry blocker isradipine (PN 200-110) were assessed in 20 middle-aged male patients with essential hypertension. The study was double-blind placebo-controlled with a crossover design. Isradipine or placebo tablets were titrated from 2.5, 5, and 7.5 mg b.i.d. every 3rd week to achieve a diastolic blood pressure of less than or equal to 90 mm Hg. The renal parameters were assessed 2-4 h after dosing. Despite a decrease in diastolic blood pressure (91 vs. 104 mm Hg, p less than 0.001) the renal plasma flow increased (465 vs. 394 ml/min, p less than 0.05). The glomerular filtration rate was unchanged and the filtration fraction was reduced (0.21 vs. 0.23, p less than 0.05). The plasma renin activity increased (0.71 vs. 0.51, p less than 0.05). The patients probably did not retain sodium because the body weight was unchanged. Rather, long-term treatment with isradipine was associated with a repetitive postdose increase in natriuresis (0.45 vs. 0.34 mmol/min, p = 0.06).
Blood Pressure↗
A longitudinal study of circulating progesterone, oestradiol, hCG and hPL during pregnancy in type 1 diabetic mothers.
Serum progesterone, oestradiol, human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) were determined serially throughout 27 pregnancies in insulin-dependent diabetic patients from Newcastle (UK), 15 such patients from Stockholm (Sweden) and in 69 normal women having uncomplicated pregnancies. Mean progesterone, oestradiol and hCG concentrations were somewhat higher in the diabetic women during the third trimester but hPL values were not different from normal. The increased hormone concentrations did not relate to the increased birthweights or placental weights in the diabetic women. It is suggested that the usual physiological endocrine changes during normal pregnancy are relatively undisturbed by insulin-dependent diabetes or the degree of diabetes control achieved.
Adult↗
Factors influencing neonatal morbidity in gestational diabetic pregnancy.
The influence of obstetric factors and indices of maternal blood glucose control on neonatal morbidity was examined in 261 women with gestational diabetes. A reference group of 218 women, matched for age and day of delivery, within 1 week, was used for comparison. Perinatal morbidity was significantly more frequent in the gestational diabetic pregnancies (23%) than in the reference group (13%), whereas the occurrence of large-for-gestational-age infants was not different between the groups. Infants born to women with gestational diabetes were categorized to a no-morbidity group (n = 200) and a morbidity group (n = 61). The group with morbidity had significantly shorter gestational age at delivery, higher frequency of caesarean section, higher maternal pre-pregnancy weight and higher area under the glucose tolerance curve. There was no significant difference in third-trimester blood glucose between the groups. Discriminant analysis revealed that the most significant influence on neonatal morbidity was gestational age at delivery. After correction for this factor the only factor with added significance for neonatal morbidity was maternal pre-pregnancy weight. The present study clearly illustrates that other factors beside blood glucose control are of importance for neonatal outcome in gestational diabetic pregnancy.
Adult↗
Central sympathoinhibitory effect of ketanserin in the spontaneously hypertensive rat.
The sympathoinhibitory effects of ketanserin were investigated in the spontaneously hypertensive rat. In conscious rats ketanserin (0.1-10.0 mg/kg intravenously caused dose-related reductions in blood pressure and heart rate (carotid artery). The heart rate reduction was prevented by chemical sympathectomy (reserpine) and in anaesthetized rats the heart rate reduction was correlated to a reduction in the directly recorded preganglionic sympathetic activity in the left renal nerve. Ketanserin had no presynaptic effects on the sympathetic nerve terminals as evidenced by the lack of effect on the tachycardia induced by electrical stimulation of the sympathetic outflow in pithed rats. In rats, catecholamine-depleted by reserpine, the heart rate reduction was prevented, and in atropine-pretreated animals there was a partial blockade of the bradycardic effect. We conclude that the lack of reflexogenic tachycardia in response to the hypotension induced by ketanserin treatment is partly due to a preganglionic inhibition of sympathetic nerve activity.
Animals↗
Plasma amino acids in relation to metabolic control in insulin-dependent diabetic children.
The influence of metabolic control (estimated by blood glucose, 3-hydroxybutyrate and glycosylated hemoglobin levels) on plasma amino acids was determined in a group of 56 insulin-dependent diabetic children. A multiple correlation analysis revealed significant positive partial correlations between most amino acids and blood glucose. Alanine, methionine, tyrosine, phenylalanine and arginine showed negative partial correlations to the 3-hydroxybutyrate level. The results are consistent with the postulate that ketone body inhibition of muscle proteolysis is one of the factors regulating substrate flows during insulin deficiency.
3-Hydroxybutyric Acid↗
Malignant lymphomas and occupational exposures.
The effects of potential risk factors for Hodgkin's disease (HD) and for non-Hodgkin lymphomas (NHL) were evaluated in a case-referent study encompassing 54 cases of HD, 106 cases of NHL, and 275 referents, all alive. Exposure information was obtained by questionnaires posted to the subjects. Crude rate ratios were increased for various occupational exposures including solvents, welding, wood preservatives, phenoxy acids, and fresh wood (sawmill workers, lumberjacks, paper pulp workers). After further analyses based on logistic regression occupational exposures to welding and creosote remained as significant risk factors for HD. For NHL, occupational exposures to solvents, phenoxy acids, and creosote but also work as carpenter or cabinet maker and contacts with pets (other than dogs, cats, and birds) were associated with significantly increased risks.
Adult↗
The effects of altered nutritional status upon insulin-like growth factors and their binding proteins in neonatal rats.
To investigate the role of nutrition in the regulation of IGFs during the perinatal period, 10-d-old rats were infused intravenously with various concentrations of nutrients for 24 h. Breast-fed litter mates served as controls. The effect of caloric intake on concentrations of IGF-I and IGF-II as well as IGF-binding proteins in serum, liver, and brain of neonatal rats was studied. A total of 45 rats from 10 litters was infused with solutions ranging from a caloric intake of 0 (saline) to 75% (glucose, amino acids, and lipids) of the estimated intake of control rats. In serum, both IGF-I and -II concentrations fell markedly in response to fasting. Serum IGF-II levels were linearly related to caloric intake in the pooled data from all groups. Concentrations of IGF-II, but not IGF-I, in liver and brain were depressed by caloric restriction. In contrast to the fall in IGF concentrations, activity of IGF-associated binding proteins rose in serum and in liver cytosol 2- to 4-fold in response to decreased nutrient intake. In serum, but not liver, the rise in binding protein activity was inversely related to to caloric intake. In liver, cytosol, but not serum, the rise in binding protein activity was inversely related to total serum amino acid concentration. Thus, IGF concentrations in preweanling rats change in response to alterations of nutrient intake. The fasting induced decrements in IGF levels, as well as the elevations in IGF-associated binding protein activity, may serve as a protective mechanism to depress growth in times of caloric restriction.
Animals↗
Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity.
Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7-58 pM) vs. 3.8 pM (less than 1.2-28 pM) in control subjects (P less than .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60-237 pM) vs. 118 pM (71-175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a beta-cell more vulnerable to destruction, or it could reflect previous beta-cell damage that does not lead to IDDM.
Adolescent↗
The effect of arachidonic acid and its metabolites on acid production in isolated human parietal cells.
The effect of arachidonic acid and its metabolites on the histamine-stimulated acid production in human isolated parietal cells provenient from endoscopic biopsies was examined. 14C-aminopyrine (14C-AP) accumulation in the parietal cells was used for evaluation of acid production. Histamine dose-dependently increased AP uptake. Histamine stimulation (taken as 100% at 10(-5) M) was significantly inhibited by prostaglandin (PG) E2 to 66 +/- 7% at 10(-8) M, 42 +/- 8% at 10(-6) M, and 13 +/- 10% at 10(-4) M (mean +/- SEM, n = 10). PGF2 alpha, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10(-5)-10(-4) M). Leukotriene (LT) B4 and LTC4 were without effect. The basal acid production (taken as 0%) was lowered significantly by 10(-6) M arachidonic acid to -20 +/- 7.4% (p less than 0.02, n = 10), and the histamine-stimulated (10(-6) M) acid production from 100% to 64 +/- 7.2% (p less than 0.001, n = 10). Aspirin (10(-3) M) increased basal (45 +/- 9.6%, p less than 0.001, n = 10) and histamine-stimulated (10(-6) M) acid production (164 +/- 16.3%, p less than 0.001). It is concluded that PGE2, the major product from arachidonic acid metabolism in the human gastric mucosa, is a significant inhibitor of the histamine-stimulated human parietal cell and may, in humans, play a role as a local physiologic inhibitor of acid secretion.
Adult↗
Magnetic resonance imaging and aneurysm clips. Magnetic properties and image artifacts.
The magnetic properties of 12 different types of aneurysm clip were investigated in order to identify which clips allow postoperative magnetic resonance (MR) imaging without risk. Clip-induced MR artifacts were also quantitatively studied using a geometrical phantom. Nonferromagnetic aneurysm clips like the Yaşargil Phynox, Sugita Elgiloy, and Vari-Angle McFadden clips do not appear to contraindicate MR studies performed with a FONAR beta-3000M imager. There is no clip movement upon introduction of the phantom into the MR imager, and the image artifacts caused by the clips are so limited that patients harboring such clips may well be considered for MR imaging. This examination may reveal information not obtainable by any other radiological modality.
Aneurysm↗
[Medical microbiology in Lund. The first documents and practitioners].
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Academies and Institutes↗
Adrenaline infusion in man increases muscle sympathetic nerve activity and noradrenaline overflow to plasma.
This study was conducted to determine if muscle sympathetic nerve activity (MSA) and/or the neuronal release of noradrenaline per impulse are modulated by adrenaline in the physiological plasma concentration range. We gave step-wise infusions of adrenaline (0.05-0.6 nmol/kg per min) to 10 healthy young men and measured: intra-arterial blood pressure; heart rate; central venous pressure (CVP); efferent MSA (microneurography in the peroneal nerve); arterial (brachial artery) and femoral venous plasma concentrations of noradrenaline, and the spillover of noradrenaline to arterial and venous plasma (radiotracer infusion). The infusion of adrenaline caused a fall in diastolic blood pressure and tachycardia, and was associated with increases in MSA and noradrenaline spillover. These observations suggest that part of the adrenaline-induced increase in transmitter release is due to enhanced nerve impulse activity, but such a conclusion rests on the absence of diffusion limitations from the site of noradrenaline infusion into the blood stream. After termination of adrenaline infusion the tachycardia and elevated plasma noradrenaline levels persisted, but these changes were probably due mainly to a profound increase in nerve activity. Concurrently, there was a reduction in CVP which may have triggered the increase in efferent sympathetic nerve activity. Infusions of adrenaline did not influence the clearance of noradrenaline from arterial plasma, but the fractional extraction over the leg was moderately reduced, indicating that more arterial noradrenaline is recovered in venous plasma during adrenaline infusion. The present data suggest that the reasons for the adrenaline-induced increase in noradrenaline release are complex, but they are consistent with the hypothesis that stress levels of adrenaline enhance sympathetic nerve activity, and that circulating adrenaline may modulate both haemodynamic and neural responses to stress.
Adult↗