bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of prostaglandins and leukotrienes by human lung tissue in vitro after activation by the calcium ionophore A23187
Authors: ZIJLSTRA F. J. , NAAKTGEBOREN M. , MONS H. , VINCENT J. E. 
Published: March 2008

Abstract. The formation of metabolites of arachidonic acid by the cyclo‐oxygenase and lipoxygenase pathways were determined in human lung tissue, obtained from surgery. In this measurement the chopped tissue was incubated with the calcium ionophore A23187. Formation of metabolites from [1‐14C] arachidonic acid was also determined. The metabolites were extracted, separated by HPLC and identified by measurement of the absorption spectrum at 280 nm, radioactivity, biological activity and by radioimmunoassay.6‐keto‐prostaglandin F1α (6‐ketoPGF1α), the metabolite of prostacyclin, is the cyclo‐oxygenase product present in the highest amount (400±49 ng g‐1), followed by PGD2 (162±59 ng g‐1) thromboxane B2 (102 ± 32 ng g‐1) PGE2 (104 ± 46 ng g‐1) and PGF2α (58 ± 26 ng g‐1). The amounts of the lipoxygenase products are: leukotriene B4 (LTB4), 163 ± 100 ng g‐1; LTC4, 63±31 ng g‐1 and LTE4 121±34 ng g‐1. From [1‐14C] arachidonic acid higher amounts of the cyclooxygenase than of the lipoxygenase products were formed, with the exception of PGE2.The effects of several of these substances on the contraction of human small airway smooth muscle were measured. The contractions, induced by equivalent amounts of LTC4 and a synthetic analogue of thromboxane T x A2 were approximately one hundred times those induced by PGD2, PGF2α and histamine.These results suggest that thromboxane A2 and LTC4 are the most important arachidonic acid metabolites that induce bronchoconstriction in the human lung.
Oral E2 prostaglandins affect endocrine cell populations in the gastric antrum of the rat
Authors: URIBE A. , GRIMELIUS L. , THEODORSSON L. E. , RIIS‐ANGELO L. , JOHANSSON C. 
Published: March 2008

Abstract. The aim of the present study was to investigate antral endocrine cell populations and tissue and circulating hormone levels following a 4‐week oral regimen with prostaglandin E2 (25, 250 and 5000 μg kg‐1 b.i.d.) or a stable methyl analogue (5 and 50 μg kg‐1 b.i.d.). Epithelial hyperplasia of the gastric antrum was observed with the highest dose of prostaglandin E2 and both doses of the analogue, as evaluated by stereological methods and conventional cell count. The treatments significantly affected the endocrine cell population. Somatostatin‐immunoreactive cells were increased in proportion to the increased epithelial cellularity and plasma levels of somatostatin were increased in parallel. The tissue content of somatostatin‐like immunoreactivity differed according to the extraction procedure used, and was significantly higher than controls in specimens extracted in neutral water. In the neutral extracts an immunoreactive somatostatin of unidentified molecular structure dominated quantitatively over somatostatin 14 and 28, which were the major components in acetic acid extracts.The serotonin‐immunoreactive cell population was also significantly increased by natural prostaglandin E2 and the analogue but the gastrin cell population was not significantly affected by treatments. Accordingly, no significant changes were observed in tissue or plasma gastrin levels.It is concluded that the epithelial hyperplasia of the antral epithelia produced by E2 prostaglandins is associated with selective changes of endocrine cell populations. The changes were proportional to the increases of epithelial cellularity and required quantitative determination of the total antral volume to be detected. It may seem surprising that the most consistent finding in the hyperplastic antral mucosa was an increase of somatostatin‐immunoreactive cell population, and elevated tissue and plasma concentrations of this peptide, which has anti‐trophic actions on gastrointestinal epithelia. It is possible that somatostatin increments contribute to restrict the hyperplasia and are responsible for the reduced new cell production observed in prostaglandin‐induced hyperplasia of gastric and intestinal epithelia.
Effects of 3‘‐azido‐3’‐deoxythymidine (AZT) on short‐term cultured human peripheral blood lymphocytes
Authors: TAURIS P. , MØLLER B. , PETERSEN C. MUNCK , BLACK F. T. 
Published: March 2008

Abstract. Although an optimal dose‐regimen has still not been established, the antiviral drug 3‘‐azido‐3‘‐deoxythymidine is known to improve the clinical condition of patients suffering from acquired immunodeficiency syndrome and acquired immunodeficiency syndrome‐related complex.The drug effect has mainly been assessed in terms of survival time and/or immunological parameters.One of the most prominent immunological features associated with immunodeficiency virus infection is a persistant hypergammaglobulinaemia due to in vivo polyclonal B‐lymphocyte activation. In vitro this is reflected by a hyporesponsiveness of peripheral blood B‐lymphocytes to mitogen and antigen induced activation.The present paper deals with the in vitro impact of 3′‐azido‐3′‐deoxythymidine on the immunoglobulin secretion in short‐term cultures of peripheral blood lymphocytes. Twenty‐four human immunodeficiency virus antibody positive (seropositive) and 24 antibody negative (seronegative) individuals were studied. In addition, T‐ and B‐cell proliferation and the distribution of cell surface markers were determined in 3′‐azido‐3′‐deoxythymidine‐supplemented cultures of peripheral blood lymphocytes from eight seronegative subjects.At concentrations similar to those reported in clinical trials, 3′‐azido‐3′‐deoxythymidine was found to suppress the mitogen and antigen induced proliferation of T‐cells from seronegative subjects. In contrast, B‐cell proliferation and the distribution of membrane markers appeared to be unaffected by the drug. Furthermore, 3′‐azido‐3′‐deoxythymidine did not alter the i vivo immunoglobulin secretion capacity in autologous or allogeneic cultures of lymphocytes from seropositive subjects.In human immunodeficiency virus‐infected individuals the number of unactivated, circulating B‐cells is significantly reduced. The present results indicate that the functional capacity of these ‘remaining’ cells may be seriously impaired during antiviral therapy with 3′‐azido‐3′‐deoxythymidine.
Intravenous and subcutaneous administration of a long‐acting somatostatin analogue: effects on glucose metabolism and splanchnic haemodynamics in healthy subjects
Authors: ERIKSSON L. S. , WAHREN J. 
Published: March 2008

Abstract. The effect of SMS 201–995, a long‐acting somatostatin analogue, on splanchnic blood flow and glucose metabolism, was investigated in five groups of healthy subjects. Groups A (n= 4), B (n= 5), C (n= 5) and D (n= 5) were studied before, during and after a 60‐min intravenous infusion of SMS (1.7, 0.8,0.2 and 0.1 μg min‐1, respectively). Group E (n=6) was investigated before and for 6 h after a subcutaneous injection of 25 μg of SMS. The splanchnic blood flow decreased by 20–25% in all groups in response to SMS and remained low during the entire observation periods. Arterial concentrations of glucose showed a 15–20% decline during SMS infusion in Groups A and B (P<0.05–0.01) and a less pronounced decrease in the other groups. Fifteen minutes after the end of infusion the glucose levels started to rise and in group A, the levels were significantly higher than basal (+25%, P<0.05–0.01) at 90–180 min after the end of infusion. The net splanchnic glucose production, determined in groups A and B, decreased by 65–75% in response to SMS infusion. Towards the end and immediately after the infusions, however, the net glucose output increased, but decreased again at 30–60 min after the end of infusion. Arterial, insulin and glucagon concentrations decreased significantly during infusion in all groups. This decline was more pronounced for insulin (50%) than for glucagon (20–25%) and insulin concentrations remained low for a longer period after the end of infusions. After subcutaneous injection both insulin and glucagon levels were low for up to 6 h. Arterial ammonia concentrations decreased and the concentrations of threonine, serine, glutamine, glycine, valine, leucine, phenylalanine, lysine and histidine all rose after i.v. infusion of SMS.It is concluded that SMS exerts a similar, but more prolonged, influence on splanchnic blood flow and the secretion of insulin and glucagon as compared to somatostatin. In addition, the high circulating levels of glucose after the end of infusion, in the face of low splanchnic glucose output, suggests that SMS has a direct effect on peripheral glucose uptake.
Ligand‐specific and non‐specific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP)
Authors: HIRSCHEL‐SCHOLZ SUSANNE , SIEGENTHALER G. , SAURAT J.‐H. 
Published: March 2008

Abstract. Retinoic acid (RA) is bound intracellularly by a specific, low molecular weight protein (CRABP), that is unrelated to its nuclear receptor and whose function and regulation are still unknown. In the present study we were able to obtain an in vivo modulation of CRABP by different stimuli in one of the major target organs of RA: the human skin. We found increased CRABP after daily application during 4 days of natural or synthetic retinoids (RA, acitretin, isotretinoin, Ro137410, retinol), that have either a high affinity to CRABP or can be transformed into RA. Only Ro150778 with no affinity and no reported transformation had no effect. No macro‐ or microscopical changes could be observed with any of the tested compounds. Induction of inflammatory and hyperproliferative changes in the skin by topical dithranol treatment, UVB irradiation or scotch tape stripping also induced a significant increase of CRABP 3 days after exposure. Topical diflucortolone showed not only a tendancy to decrease intrinsic CRABP levels, but significantly reduced the retinoid stimulated rise of CRABP.Thus we conclude that the increase of CRABP in a fully differentiated adult tissue seems to be a biological phenomenon following processes of inflammation and proliferation with a lag of several days, while retinoids seem to be able to induce such a rise independently of, or before, the appearance of such processes. Corticosteroids seem to be inhibitors of this reaction. We discuss the hypothesis that CRABP might function as an intracellular ‘buffer’ in the case of RA overload.
The glomerular sieving of pepsinogen A and C in man
Authors: KATE R. W. TEN , PALS G. , RES J. C. J. , KAMP G. J. VAN , VERHEUGT F. W. A. , PRONK J. C. , DONKER A. J. M. , ERIKSSON A. W. , MEUWISSEN S. G. M. 
Published: March 2008

Abstract. Pepsinogen A (PGA) and pepsinogen C (PGC) are negatively charged, low molecular weight (LMW) proteins with a striking difference in renal handling: PGA (molecular weight 43 500 daltons) shows a high fractional excretion while the fractional excretion of PGC (molecular weight 40 500 daltons) is low, presumably due to tubular reabsorption. As these data suggest a high glomerular sieving of pepsinogens, we assessed the glomerular sieving coefficient (GSC) of PGA, PGC and several other proteins from their renal extractions'. For this purpose blood samples were obtained simultaneously from the aorta (A) and right renal vein (V) in nine patients undergoing an elective heart catheterization.After correction of the A‐V differences for diuresis with the A‐V difference of transferrin, GSCs (± SEM) for PGA and PGC were 0.90±0.14 and 0.85 ± 0.17, respectively, GSC of β2‐microglobulin being 0.90 ± 0.12. For albumin and IgG, known to have a low GSC, low values were found.It is concluded that the GSC of a LMW protein in man can be calculated from both its A‐V difference over the kidney and the A‐V difference of an inert marker with a GSC of 1, provided they are corrected by the A‐V difference of an inert marker with a GSC of 0. Our results demonstrate that PGA and PGC are almost freely filtered through the glomerular basement membrane despite their size and negative net molecular charge.
Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate
Authors: STEINMETZ A. , THIEMANN ELISABETH , CZEKELIUS P. , KAFFARNIK H. 
Published: March 2008

Abstract.To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblottrag and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the aduit, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the 62 allele and lowest in individuals expressing apoE4, and vice versa for apoB.We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constantin uteroenvironment.
Molecular analysis of acute intermittent porphyria in a Finnish family with normal erythrocyte porphobilinogen deaminase
Authors: GRANDCHAMP B. , PICAT C. , KAUPPINEN R. , MIGNOTTE V. , PELTONEN L. , MUSTAJOKI P. , ROMÉO P. H. , GOOSSENS M. , NORDMANN Y. 
Published: March 2008

Abstract. Porphobilinogen deaminase, the third enzyme of the haem biosynthetic pathway, is encoded by two distinct mRNA species expressed in a tissue‐specific manner from a single gene. These two mRNAs are transcribed from two promoters and only differ in their first exon. An inherited deficiency or porphobilinogen deaminase in man is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease.In the present report, we describe the molecular abnormality responsible for a variant form of acute intermittent porphyria where the enzyme defect is restricted to non‐erythroid cells. Upon cloning and sequencing the mutant allele of a patient from a large Finnish kindred, a single‐base substitution within the 5′‐splice donor sequence of intron 1 was found at the last position of exon 1 (CGCT).The identification of this mutation allowed us to detect asymptomatic gene carriers among family members using in vitro amplification of DNA and hybridization of the target sequence to allele‐specific oligonucleotides.
The effect of testosterone replacement on plasma lipids and apolipoproteins
Authors: JONES D.B. , BILLET J.S. , PRICE W.H. , EDWARDS C.R. W. , BEASTALL G.H. , HIGGINS B. , SHEPHERD J. , HORN D. B. , WENHAM P. R. , SWEETING V. M. 
Published: March 2008

Abstract. Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later.Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL‐cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL‐cholesterol, HDL‐cholesterol subfractions 2 and 3 or in apoplipoproteins A‐I, A‐II or B.A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs=0.61; P < 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs= ‐0.56; P < 0.005) but not with the other lipid parameters.Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.
Natural occurrence of IgE antibodies to peptide hormones in man
Authors: KHALAF A. ‐N. , KERP L. , SCHLIEBS B. , JÄGLE M. , PETERSEN K.‐G. 
Published: March 2008

Abstract. IgE antibodies to peptide hormones or their fragments were investigated using specific radioaller‐gosorbent tests. Ninety‐six sera were obtained from otherwise healthy individuals with a positive RAST to at least one common allergen and without previous contact to exogenous hormones. Total serum IgE was normal (< 300 ng ml‐1) in 41 and elevated in 55 sera. Only one serum with normal total IgE had reagins to proinsulin. In sera with elevated total IgE positive tests (> 8 times background) were observed frequently: hGH 9.1%, GHRH1–44 5.5%, GHRH1–29 12.7%, erythropoietin 10.9%, human calcitonin 14.6%, salmon calcitonin 1.8%, ACTH 5.5%, insulin 14.6%, proinsulin 7.3%, insulin A chain 1.8%, insulin B chain 18.2%, C‐peptide 9.1%, and IGF 9.1%.The data show natural occurrence of reagins to peptide hormones in atopic persons. A risk at exposure to these peptides may exist in about 1% of the general population.
Relationship between the metabolism of antipyrine, hexobarbital and theophylline in patients with liver disease as assessed by a ‘cocktail’ approach
Authors: SCHELLENS J. H. M. , JANSSENS A. R. , WART J. H. F. VAN DER , VELDE E. A. VAN DER , BREIMER D. D. 
Published: March 2008

Abstract. Antipyrine (AP), hexobarbital (HB) and theophylline (TH) were administered simultaneously (‘cocktail’ design) to 24 patients with various types of liver disease. Clearance (CI) of AP, HB and TH and formation clearance of the AP‐metabolites 3‐hydroxy‐methylantipyrine (HMA), norantipyrine (NORA) and 4‐hydroxyantipyrine (OHA) were determined and correlation coefficients and orthogonal least‐squares regression lines calculated between the clearance and formation clearance parameters. The results were compared with those obtained in a study in which the same ‘cocktail’ was administered to 26 healthy control subjects.In the patients ClAP, ClHB and CITH were 23.0±14.3 ml min‐1, 206±128 ml min‐1 and 39.9 ± 26.1 ml min‐1 respectively. All values were considerably lower than those found in the control subjects. With regard to AP metabolism preferential impairment of NORA formation was observed. Relatively high correlation coefficients were found between ClAP, ClHB and C1TH, which suggests, like the results of orthogonal regression analysis, a strong correlation between total metabolism of these probe drugs. Therefore it is likely that impairment in oxidation in patients with liver disease not only leads to reduction in clearance but also to reduced substrate selectivity of cytochrome P‐450 isozymes.
Adenosine receptor mediated stimulation of ventilation in man
Authors: JONZON B. , SYLVÉN C. , BEERMANN B. , BRANDT R. 
Published: March 2008

Abstract. We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 ± 1.9 1 min‐1 to 42.5 ± 4.7 1 min‐1 in a dose‐dependent manner. The adenosine receptor antagonist theophylline, 58.3 ± 3.3 (mean±SEM) µniol 1‐1 plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation.The respiratory stimulation started before chest pain and cardiovascular effects such as AV‐block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on afferent pathways.
Neuro‐humoral control of insulin secretion
Authors: BOBBIONI‐HARSCH E. , JEANRENAUD B. 
Published: March 2008

Abstract. Hypothalamic extract from normal rats was shown to contain a principle able to stimulate insulin secretion both in vivo and in vitro.This substance, whose peptidic nature was demonstrated by enzymatic digestion, has a molecular weight of about 1000 Daltons. An active release of this peptide was obtained when incubating hypothalamic fragments under appropriate stimulatory conditions (i.e. KC1 50 mmol 1‐1 in the incubation medium) (i.e. molecular weight and insulin secretion stimulating activity) similar to the hypothalamic peptide was evidentiated in the plasma of normal rats. Since manipulations of hte hypothalamus (i.e. electrical lesions or stimulations) could respectively decrease or enhance the plasma concentration of this substance, the hypothalamic origin of the insulin secretion stimulating principle present in the plasma was strongly suggested. The possible participation of this hypothalamic peptide to the neural control of insulin secretion is suggested.
Hormones as regulators of pancreatic secretion in man
Authors: ADLER G. , BEGLINGER C. 
Published: March 2008

SummaryAt the beginning of the century, Pavlov Suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss & Starling published their experiments on secretin and claimed that the nervous regulation is ‘superfluous and improbable’. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural. hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretin modulating the response.
Interruption of the entero‐pancreatic axis: effects of induced malabsorption
Authors: CASPARY W. F. 
Published: March 2008

Abstract. The rate of intestinal absorption depends not only on the mode of ingestion and the chemical nature of nutrients ingested, but largely on the regulatory gastrointestinal motility processes and the digestive‐absorptive capacity of the gastrointestinal tract.This review is mainly concerned with modes of nutrient absorption and their regulatory mechanisms.Modulation of intestinal absorptive processes possibly seems to be a valuable therapeutic strategy in various metabolic (diabetes mellitus) and gastrointestinal diseases.