bluuebunny/crossref_metadata_2025 huggingface dataset:
Basal cyclic AMP levels in human blood mononuclear cells
Authors: SVENSON M. , PERMIN H. , WIIK A.
Published: March 2008

Abstract. Basal cyclic AMP levels in blood mononuclear cells from healthy human donors has been studied. A great variation in cyclic AMP content ranging from below 2 to 20 pmol 10‐6 cells was seen. Incubation of the cells at 37°C mostly showed a time‐dependent decrease in basal cyclic AMP, levelling off after 16 h. When treated synchronously, cells from blood from the first sample of blood sampling contained more cyclic AMP than that of later samples. Presence of adenosine deaminase, theophylline or indomethacin influenced cyclic AMP concentrations in a non‐consistent manner. Variations in cyclic AMP content may in some individuals be ascribed to early increase of cyclic AMP, in others to a progressive reduction in basal cyclic AMP during blood sampling, cell preparation and incubation.
Studies of lipoprotein metabolism in a patient with fish‐eye disease
Authors: TURNER P. R. , CARLSON L. A. , CORTESE C. , RAO S. , MARENAH C. B. , MILLER N. E. , LEWIS B.
Published: March 2008

Abstract. In the rare familial disorder fish‐eye disease, hypertriglyceridaemia is associated with elevated levels of very‐low‐density lipoprotein (VLDL) and enrichment of low‐density lipoprotein (LDL) with triglyceride. The kinetic basis of the dyslipoproteinaemia was investigated by studying the metabolism of the apolipoprotein‐B moeity of VLDL, intermediate‐density lipoprotein (IDL) and LDL in a 68‐year‐old woman with this condition. The major kinetic abnormality was a pronounced reduction in the rate of fractional conversion of VLDL‐B to IDL‐B and of IDL‐B to LDL‐B, suggesting that the dyslipoproteinaemia represents accumulation in plasma of partly degraded products of VLDL metabolism. This kinetic disorder has features in common with type‐III hyperlipoproteinaemia. In studies in vitro no defect in the enzyme, activator or substrate components of the lipoprotein lipase or hepatic lipase systems was observed.
Quantitation of bilirubin conjugates with high‐performance liquid chromatography in patients with low total serum bilirubin levels
Authors: JANSEN PETER L. M. , CUYPERS H. THEO , PETERS WILBERT H. M.
Published: March 2008

Abstract. Bilirubin mono‐ and diconjugates were determined by alkaline methanolysis and high‐performance liquid chromatography (HPLC) in serum from patients with metastatic liver disease and liver cirrhosis. Conjugates could be detected and quantitated at normal or low total bilirubin levels. Comparison with serum alkaline phosphatase activity revealed that in cirrhosis bilirubin conjugates were sometimes detectable at normal or slightly elevated alkaline phosphatase activities. In patients with metastatic liver disease alkaline phosphatase activity was a more sensitive indicator.

In normal controls and in patients with Gilbert's syndrome no bilirubin conjugates were detected whereas serum of patients with haemolysis contained conjugated bilirubin. Therefore HPLC appears to be an excellent method to diagnose Gilbert's syndrome. In liver cirrhosis HPLC is a useful liver function test.
Experimental skeletal muscle damage: the nature of the calcium‐activated degenerative processes
Authors: JACKSON M. J. , JONES D. A. , EDWARDS R. H. T.
Published: March 2008

Abstract. The role of calcium‐activated degenerative processes in the efflux of enzyme from experimentally damaged mouse muscle has been studied using an isolated mouse soleus muscle preparation. Inhibition of mitochondrial activity with dinitrophenol or sodium cyanide was found to cause a large efflux of enzyme. This was largely prevented by withdrawal of the extracellular calcium suggesting that mitochondrial calcium overload does not play a major role in the damage leading to enzyme efflux.

Treatment of the muscles with a variety of protease inhibitors had no effect on the enzyme efflux from muscles following exhaustive contractile activity indicating that activation of protease activity is not a major factor in the damaging process. Certain inhibitors of phospholipase‐A activity (i.e. dibucaine, chlorpromazine and mepacrine) have been found to significantly reduce the enzyme efflux following treatment of the muscles with dinitrophenol, although other phospholipase inhibitors were without effect.

It is suggested that the changes in muscle membrane permeability leading to enzyme efflux following experimental muscle damage are probably the result of calcium‐mediated activation of phospholipase A leading to changes in membrane phospholipid metabolism.
Degradation of amyloid A and serum amyloid A by red blood cell haemolysate in patients with familial mediterranean fever
Authors: SHAINKIN‐KESTENBAUM RUTH , WINIKOFF YEHUDIT , ZIMLICHMAN SHULAMIT , GORODISCHER RAFAEL , PRAS MORDECHAI
Published: March 2008

Abstract. Enzymatic activity for the degradation of serum amyloid A (SAA) and amyloid A (AA) was detected in erythrolysates of normal subjects and patients with familial mediterranean fever. A significant difference between the activity of normal subjects and patients was not found. Serum inhibited the SAA (but not the AA) haemolysate proteolytic activity. Interindividual variation in the susceptibility of SAA to degradation by RBC haemolysates was shown. The original digestible fraction of SAA became gradually resistant to proteolytic cleavage over a 9 month period while the susceptibility of AA to degradation remained unchanged in this time period.

These findings suggest that enzymatic degradation of SAA depends on the source of SAA, as well as inhibitory activity in serum.
Familial benign hypercalcaemia: a possible abnormality in calcium transport by erythrocytes
Authors: HOARE S. F. , PATERSON C. R.
Published: March 2008

Abstract. The fundamental biochemical abnormality in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) is unknown. It seemed possible that, since the kidneys and the parathyroid glands are insensitive to the high extracellular calcium levels, a general disorder of the regulation of the calcium pump on the plasma membrane is present. We obtained evidence suggesting that active calcium efflux by erythrocytes from patients with FBH (85·7 pL 4·5 μmol l‐1 min‐1) is higher (P < 0·005) than that by erythrocytes from control subjects (78·6 pL 4·1 μmol l‐1 min‐1) or from patients with primary hyperparathyroidism (77·5 pL 5·2 μmol l‐1 min‐1, P < 0·05). Calcium influx into erythrocytes was normal in FBH and in primary hyperparathyroidism.
Impermeability of the blood‐cerebrospinal fluid barrier to 1‐deamino‐8‐D‐arginine‐vasopressin (DDAVP) in patients with acquired, communicating hydrocephalus
Authors: SØRENSEN PER SOELBERG , VILHARDT HANS , GJERRIS FLEMMING , WARBERG JØRGEN
Published: March 2008

Abstract. The passage of the vasopressin analogue, 1‐deamino‐8‐D‐arginine‐vasopressin (DDAVP) into the cerebrospinal fluid (CSF) following intravenous (i.v.) administration was studied in human subjects. After i.v. injection of DDAVP, resulting in plasma levels exceeding normal plasma concentrations of vasopressin (AVP) by 100‐fold, serial blood and ventricular CSF specimens were sampled during 2 h. Plasma and CSF were analysed by radioimmunoassay using two different AVP antisera: one specific against natural AVP and another cross‐reacting 100% with DDAVP. No changes in the joint concentrations of DDAVP + AVP in CSF were found following i.v. infusion of DDAVP when compared with the concentration before the infusion. Neither was any difference between CSF concentrations of AVP and DDAVP + AVP observed at any sampling time following the i.v. DDAVP administration. Hence, it is concluded that no measurable amounts of DDAVP can be found in the CSF for up to 2 h after i.v. administration of the peptide, and that for all practical purposes a blood‐CSF barrier to DDAVP exists.
Dissociation of the factor‐VIII complex during clotting: role of thrombin and phospholipids
Authors: MUNTEAN W. , ROTHWANGL H. J.
Published: March 2008

Abstract. To study the dissociation of the two moieties of the factor‐VIII complex during clotting, plasma, concentrate and serum were chromatographed on 4% agarose. In plasma and concentrate factor‐VIII coagulant activity (VIII C), factor‐VIII coagulant antigen (VIII C:Ag), and factor‐VIII‐related antigen (VIII R:Ag) eluted together in the void volume, but some VIII C: Ag eluted after the void volume. The amount of VIII C:Ag eluting after the void volume was made smaller by adding proteinase inhibitors. In serum nearly all VIII C:Ag eluted after the void volume.

From factor‐VIII complex immunoadsorbed by means of an antibody against VIII R:Ag no VIII C:Ag was dissociated by thrombin or by thrombin and physiologic CaCl2 concentrations. Radiolabelled human thrombin did not bind to the VIII C:Ag of immunoadsorbed factor‐VIII complex. VIII C:Ag displaying VIII C was dissociated from immunoadsorbed factor‐VIII complex by human brain thromboplastin or by phosphatidyl‐serine.

Our results suggest that VIII C:Ag and VIII R:Ag dissociate during clotting. This dissociation seems not to be mediated by thrombin, but may be mediated by phospholipids.
Thyroid‐stimulating immunoglobulins in insulin‐dependent diabetes mellitus
Authors: BLIDDAL HENNING , BECH KARINE , JOHANSEN KLAUS , NERUP JØRN
Published: March 2008

Abstract. Increased frequencies of thyroid diseases and thyroid microsomal antibodies have been observed in insulin‐dependent diabetes mellitus. However, the exact prevalence of thyroid‐stimulating immunoglobulins has not been established. In the present study these antibodies were measured by both a radioreceptor and an adenylate‐cyclase stimulation assay.

In forty‐six patients with insulin‐dependent diabetes mellitus without endogeneous insulin production (C‐peptide concentration ≤ 0·06 nmol l‐1) the receptor assay was positive in ten and the stimulation assay in fifteen patients. The immunoglobulins of four patients inhibited the adenylate cyclase, and one of these was positive in the receptor assay. In nine patients with post‐prandial C‐peptide 0·07–0·19 nmol l‐1, five had adenylate‐cyclase‐stimulating antibodies, while none were positive in the receptor assay. Thyroid hormones and thyrotropin concentrations were not different in the forty‐six patients without endogenous insulin production with thyroid‐stimulating immunoglobulins compared with patients without these antibodies. Patients with thyroid‐stimulating immunoglobulins required a daily median amount of 0·71 IE of insulin kg‐1 compared to median of 0·57 IE kg‐1 in patients without these antibodies (P < 0·03), despite a similar degree of diabetic regulation.

The level of tri‐iodothyronine was correlated to the antibody level in patients with adenylate‐cyclase‐stimulating antibodies. While the prognostic and possibly pathogenetic importance of these antibodies in Graves' disease have been established, their significance in insulin‐dependent diabetes mellitus remains to be demonstrated.
Increased production of platelet thromboxane B2 in non‐insulin‐dependent diabetes. Relationship to vascular complications
Authors: D'ANGELO A. , MICOSSI P. , MANNUCCI P. M. , GARIMBERTI B. , FRANCHI F. , POZZA G.
Published: March 2008

Abstract. Platelet thromboxane B2 production was studied in forty‐seven non‐insulin‐dependent diabetics by incubating platelets with increasing concentrations of arachidonic acid. In comparison with thirty‐two healthy subjects, diabetics showed increased thromboxane B2 production at 0·7 mmol/l (mean: 236 pmol/108 platelets, SEM 201–277; v. 135, 105–174; P < 0·05) and at 1·0 mmol/l (673, 613–739; v. 405, 377–486, P < 0·01) but not at 0·5 mmol/l. Patients were subdivided according to the presence or absence of vascular complications. Patients without microangiopathy showed significantly greater thromboxane B2 production than healthy subjects at all the arachidonic‐acid concentrations (P < 0·02 or less). Patients with microangiopathy had platelet thromboxane production similar to that observed in healthy subjects at all the arachidonic‐acid concentrations (P > 0·30) but significantly lower than that of non‐microangiopathic patients at 0·5 (P < 0·01) and at 0·7 mmol/l arachidonic acid (P < 0·05). These results indicate that non‐insulin‐dependent diabetics have increased production of platelet thromboxane B2 only when they do not have microvascular complications.
Effect of propranolol treatment on bone mass, bone mineral content, bone remodelling, parathyroid function and vitamin D metabolism in hyperthyroidism
Authors: MOSEKILDE L. , JASTRUP B. , MELSEN F. , LUND BI. , LUND BJ. , SØRENSEN O. H. , NIELSEN H. E. , YDE H.
Published: March 2008

Abstract. The effect of propranolol 160–640 mg/day for 3 months on the accelerated loss of bone matrix and mineral in hyperthyroidism was studied in seventeen patients. A rise in serum thyroxine (P < 0·01) during the first 3 weeks was followed by a fall (P < 0·02). Serum triiodothyronine declined during the study (P < 0·02). The enhanced bone mineral mobilization and collagen turnover continued during treatment and the bone mineral content decreased 3·2% (P < 0·01). The secondary adaptive changes in serum parathyroid hormone and vitamin‐D metabolites and in renal phosphate handling stayed unchanged. Iliac crest bone biopsies after tetracycline double‐labelling showed initially a high bone turnover (P < 0·01) with a reduced amount of cortical and trabecular bone (P < 0·05). Following treatment bone formation rate decreased at both cellular and tissue level (P < 0·01). No significant changes were observed in the amount of cortical and trabecular bone.

The investigation shows that propranolol, in contrast to antithyroid medication, lacks any curative effect on the accelerated bone loss in hyperthyroidism.
Liver glycerokinase deficiency in man with hyperglycerolaemia and hypertriglyceridaemia
Authors: POMETTA D. , SUENRAM A. , WEID N. VON DER , WIDMANN J. J.
Published: March 2008

Abstract. Hyperglycerolaemia and glyceroluria is described in a patient who presented transient dietary‐induced hypertriglyceridaemia. The increased glycerol in blood and urine was related to glycerokinase deficiency as evidenced by a hepatic tissue glycerokinase activity of one tenth (4·8 times 10‐5 mmol g‐1 min‐1) of that of normoglycerolaemic subjects (5·9 times 10‐4).

As triglycerides are routinely determined by an enzymatic method after hydrolysis to glycerol, the differential diagnosis between true hypertriglyceridaemia and hyperglycerolaemia may prove difficult. Persisting ‘hypertriglyceridaemia’ despite adequate dietary and drug treatment should suggest the existence of undiagnosed hyperglycerolaemia.
Vagal influence on exocrine pancreas of alcohol‐fed and of normal dogs
Authors: SCHMIDT D. N. , JOHNSON C. D. , DEVAUX M.‐A. , SARLES H.
Published: March 2008

Abstract. A histochemical study has indicated increased activity of acetylcholine in the pancreas of chronic alcoholic dogs, and we have recently reported decreased pancreatic responsiveness to cholinergic stimulation in such dogs. This prompted us to determine, in chronic alcoholic dogs, the net pancreatic response to stimulation mediated by cholinergic nerves. Therefore, the pancreatic response to vagal stimulation by intravenous 2‐deoxy‐d‐glucose (2DG) infusion was examined in such dogs and in controls.

After 2DG, 100 mg kg‐1, significant and similar increases in protein output up to maximally 2·7 ± 0·8 and 2·3 ± 0·5 mg kg‐1 (15 min)‐1 were observed in control and alcohol‐treated dogs. A significant rise in flow rate and HCO‐3 output up to maximally 0·26 ± 0·07 ml kg‐1 (15 min)‐1 and 43 ± 13 μmol kg‐1 (15 min)‐1, respectively, occurred in the controls but was delayed in the alcoholics.

The finding in alcoholic dogs of no change in protein response to 2DG is not in favour of a primary increase of vagally mediated pancreatic protein secretion. It could, however, be compatible with a primary increase in cholinergic receptor resistance due to alcohol and secondary adaptive increase in cholinergic activities, which when combined, would yield no net change of the cholinergically mediated protein response.
Effects of cyclooxygenase inhibitors, prostaglandins F2α and I2, on isolated coeliac and basilar arteries of alloxan‐diabetic dogs
Authors: KOLTAI M. Z. , HADHÁZY P. , MALOMVÖLGYI B. , WAGNER M. , POGÁTSA G.
Published: March 2008

Abstract. The effects of prostaglandin synthetase inhibitors PGF2α and PGI2 on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan‐diabetic dogs. PGF2α (1 μmol l‐1) produced a significantly higher tone in diabetic basilar arteries (1·15 ± 0·16 mN) than in normal cerebral vessels (0·7 + 0·10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF2α did not differ. The cyclooxygenase inhibitors indomethacin (3 μmol l‐1) and suprofen (0·58 μmol l‐1) potentiated the PGF2α‐evoked contractions in all of the vessels studied. The percent potentiation was greater (50–60%) in the basilar arteries from alloxan‐treated dogs than in normal basilar vessels (22–30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration‐related relaxation in the presence of indomethacin or indomethacin + PGF2α. The relaxant potencies of PGI2 were similar in the vessels from metabolically healthy and diabetic dogs. The IC50 values for PGI2 were 11·6 ± 1·3 and 11·8 ± 1·8 nmol l‐1 in normal and diabetic basilar arteries, respectively; they were 25·4 ± 3·2 and 26·2 ± 3·9 nmol l‐1 in control and alloxan‐treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.
Immunochemical studies on an IgG lambda cryoglobulin in cold‐induced urticaria
Authors: JØRGENSEN M. , CLEMMENSEN I. , WIIK A.
Published: March 2008

Abstract. A type I cryoglobulinaemia associated with cold‐induced urticaria was demonstrated in a 64‐year‐old woman without primary disease. The cryoglobulin contained only IgG lambda as disclosed by immuno‐fixation technique. Different physicochemical studies indicated that the IgG lambda component was monomeric at temperatures above 35°C, but became polymerized below 35°C. In addition crossed immunoelectrophoresis of plasma fibronectin from the patient showed a heterogeneous precipitate at low temperatures but a homogeneous precipitate at 25°C indicating a complex formation at low temperature between IgG lambda and fibronectin. Fibronectin, however, was not essential for the cold precipitation of the cryoglobulin. The precipitation phenomenon at low temperatures was found to be a result of the physicochemical properties of the cryoglobulin itself unrelated to the antibody specificities tested.

The importance of performing the immunochemical and physicochemical techniques at low temperature (7°C) and at high temperature (35°C) to gain knowledge of the nature of the protein, is emphasized.

We conclude that only results obtained by relevant laboratory procedures might lead to correct classification and understanding of cryoglobulinaemia.
Factors affecting the concentration of free holo retinol‐binding protein in human plasma
Authors: FEX GÖRAN , FELDING PETER
Published: March 2008

Abstract. The total concentrations of retinol, retinol‐binding protein and prealbumin were determined in plasma from twenty healthy men and sixty patients with various inflammatory conditions. These concentrations were all strongly correlated to each other and lower in the patient group. The concentration of free (not prealbumin‐bound) holo retinol‐binding protein, the presumed ‘active’ supplier of retinol to the tissues, was calculated. It was found not to be decreased in the patient group. Of the measured total concentrations and their possible ratios in the whole material, the retinol/prealbumin ratio showed the strongest correlation to the concentration of free holo retinol‐binding protein. The importance of the concentration of free holo retinol‐binding protein for the vitamin A supply to the cells was supported by calculations on data from the literature showing that this concentration better than the above‐mentioned total concentrations distinguished between patients with normal and abnormal dark adaptation ability.
Lipoprotein abnormalities in patients with early primary biliary cirrhosis
Authors: ALY A. , CARLSON K. , JOHANSSON C. , KIRSTEIN P. , RÖSSNER S. , WALLENTIN L.
Published: March 2008

Abstract. In twelve females with early forms of primary biliary cirrhosis (PBC) serum lipoproteins, the intravenous fat tolerance test (IVFTT) and the lecithin: cholesterol acyl transferase (LCAT) rate were determined and compared to healthy controls. The cholestatic LDL (LP‐X) test was negative in all cases. PBC patients had lower very low density lipoprotein TG concentrations than controls and had levels of (high‐density lipoprotein) HDL‐TG, ‐cholesterol and ‐phospholipids that were about 50% higher than in controls. In PBC the HDL2‐cholesterol concentration was double but the HDL3‐cholesterol concentration was 60% of control values (P < 0·001 for both). The LCAT rate and the IVFTT value did not differ between the groups. A typical finding on agarose gel electrophoresis was the appearance of a slow‐moving α‐band. Several interpretations of these results are possible.

In PBC the hepatic lipase activity may be impaired leading to a shift of the HDL2/HDL3 relation. The transport of HDL2 to the liver lipase site may also be affected and HDL3 production reduced due to malabsorption in the intestine.
Plasma oxalate concentration and oxalate distribution volume in patients with normal and decreased renal function
Authors: PRENEN J. A. C. , MEES E. J. DORHOUT , BOER P.
Published: March 2008

Abstract. In twenty‐one patients (sixteen male, five female) with various kidney diseases including primary hyperoxaluria type I (four patients), the plasma oxalate level was calculated from the isotopically determined oxalate clearance and the chemically determined urinary oxalate excretion. The apparent oxalate distribution volume was assessed as well.

In patients with impaired kidney function (n= 12), the oxalate clearance was lower and the biological half‐life and plasma concentration were higher than in patients with normal kidney function (n= 10). No differences were found in the oxalate‐to‐creatinine clearance ratio (mean value 1·93), urinary oxalate excretion and apparent oxalate distribution volume. A linear relation was found between the oxalate and creatinine clearance, while the clearance ratio was independent of the degree of renal failure. The apparent oxalate distribution volume was 1·45 times the estimated extracellular fluid volume.

Because the isotopically determined plasma oxalate levels are lower than chemically measured ones, a quick and better estimation of plasma oxalate can be made from the urinary oxalate excretion and the creatinine clearance.
Effects of dopamine and dobutamine on the distribution of pulmonary blood flow during lobar ventilation hypoxia and lobar collapse in dogs
Authors: McFARLANE P. A. , MORTIMER A. J. , RYDER W. A. , MADGWICK R. G. , GARDAZ J‐P. , HARRISON B. J. , SYKES M. K.
Published: March 2008

Abstract. Hypoxic pulmonary vasoconstriction was induced in the left lower lobe of fifteen dogs by ventilating the lobe with 7% O2 or by absorption collapse, and the distribution of flow between the lobe and the remainder of the lung was measured with electromagnetic flow probes. The lobar to total blood flow ratio was reduced by lobar ventilation hyoxia and decreased further during lobar collapse.

In seven dogs, an infusion of 20 μg kg‐1 min‐1 of dopamine produced an increase in total blood flow, an increase in pulmonary artery pressure (P lt; 0·01), and an increase in lobar to total flow ratio (P lt; 0·05) during both hypoxic states. There was a significant fall in arterial PO2 (P < 0·01) during ventilation hypoxia. Similar changes in total and lobar to total flow ratio (P < 0·01) were observed in eight dogs given 20 μg kg‐1 min‐1 of dobutamine, but there were no changes in pulmonary artery pressure. The greater increase in total flow (+111%) resulted in a marked increase in mixed venous PO2 and no significant changes in arterial PO2 in this group of dogs. It is concluded that both drugs produce an increase in lobar to total blood flow ratio and shunt fraction, but that the mechanisms causing the redistribution of flow may differ.
Immunofluorescence detection of liver cell membrane autoantibodies using PLC/PRF/5 cells
Authors: KONING R. W. DE , DAEMEN M. , SCHUTTE B. , GEERTZEN H. G. M. , BLIJHAM G. H. , BOSMAN F. T.
Published: March 2008

Abstract. Detection of liver cell membrane autoantibodies is routinely performed by immunofluorescence testing of patient sera on rabbit hepatocyte suspensions. We have investigated the possible use of cells from the PLC/PRF/5 human hepatoma cell‐line. These cells were employed as substrate in an immunofluorescence test which was compared with the conventional rabbit hepatocyte assay. We found a close correlation between the results obtained with these different substrates on visual reading. We furthermore compared visual reading of immunofluorescence preparations with flow‐cytometrical analysis of immuno‐stained cell suspensions. The results with these different methods were largely confirmatory. The PLC/PRF/5 cells are easily available and should therefore be regarded as a highly valuable new substrate for detection of liver cell membrane autoantibodies. Flow cytometry appears to be a technically simple and reliable method for quantitative analysis.
Correlation of disease activity in systemic vasculitis with serum C‐reactive protein measurement. A prospective study of thirty‐eight patients
Authors: HIND CHARLES R. K. , WINEARLS CHRISTOPHER G. , PEPYS MARK B.
Published: March 2008

Abstract. In a prospective study over 2 years, serum C‐reactive protein (CRP) concentration and erythrocyte sedimentation rate were measured serially in thirty‐eight patients with various types of necrotizing systemic vasculitis. The CRP concentration was always elevated in patients with active vasculitis and fell rapidly in association with clinical remission induced by immunosuppression. During periods of complete remission, in the absence of any intercurrent condition, the value remained within the normal range. In contrast the sedimentation rate responded more slowly to changes in disease activity and did not necessarily reflect the level of inflammation at a particular time. These results, together with the commercial availability of rapid and precise assays for CRP, indicate that serial measurement of the serum CRP fills the urgent need for an objective index of the activity of the systemic vasculitides and their response to therapy.
Vitamin D3 uptake by the isolated perfused rat liver from lipoprotein fractions is separate from cholesterol and triglyceride uptake
Authors: ZIV EHUD , BAR‐ON HANOCH , SILVER JUSTIN
Published: March 2008

Abstract. Using the isolated perfused rat liver we examined the uptake of [14C] or [3H] vitamin D3 and [14C] triglyceries or [3H] cholesterol by the liver of normal rats, from different lipoprotein fractions, as measured by disappearance from the perfusate.

When incorporated into chylomicrons only 43% of the vitamin D3 remained in the perfusate at 60 min (i.e. 57% uptake) as compared to 68% of the triglycerides (i.e. 32% uptake). When added on very low density lipoproteins (VLDL) at 60 min 37 ± 3% (n= 6) of the vitamin D3, 38 ± 2% of the cholesterol (n= 3) (P NS), and 83 plusmn;4% of the triglycerides (n= 3) remained in the perfusate (P < 0·0005 for cholesterol: triglycerides and vitamin D3: triglycerides). For high density lipoprotein fraction (HDL) isolated perfused livers were studied with and without albumin present in the perfusate. Without albumin 19 ± 8% (n= 3) of the vitamin D3 and 43 ± 8% (n= 3) of the cholesterol remained in the perfusate at 60 min. The results with albumin present were 40 ± 1% (n= 5) of the vitamin D3 and 63 ± 4% (n= 5) of the cholesterol at 60 min (P < 0·0005). The cholesterol:cholesterol ester ratio of the VLDL fraction was 8·8:1 and of the HDL fraction 1:1·4. There was no metabolism of vitamin D3 during the 1 h perfusion. These results suggest that vitamin D3 is in equilibrium with the lipoprotein surface, and the hepatic uptake of vitamin D is a surface phenomenon independent of lipoprotein metabolism.
Effect of in vitro non‐enzymatic glycosylation of human skin collagen on susceptibility to collagenase digestion
Authors: LYONS T. J. , KENNEDY L.
Published: March 2008

Abstract. The effect of glycosylation on susceptibility of skin collagen to collagenase digestion was studied in a skin sample obtained at autopsy from the interscapular region of a 24 year old white male who had died of an acute illness and who had no history of diabetes. Homogenous suspensions of insoluble collagen were prepared, and were incubated in 50 mmol 1‐1 dextrose at pH 7·35 and 37°C for 7 days. Non‐enzymatic glycosylation measured by the weak acid hydrolysis/thiobarbituric acid method increased from 13·1 ± 1·0 (n= 5) to 45·2 ± 5·5 (n= 8) nmol fructose per 10 mg collagen (P < 0·001).

Digestion of collagen using clostridial collagenase was monitored by measuring (a) hydroxyproline content and (b) absorption at 206 nm of the supernatant after centrifugation to remove substrate. The rate of digestion was similar in glycosylated and control collagen. We conclude that the ketoamine link formed in non‐enzymatic glycosylation does not increase the resistance of collagen to enzymatic digestion. The possibility remains that subsequent rearrangement of this link could be important in this respect.
Duodenal gamma‐glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology
Authors: SEITZ H. K. , VELASQUEZ D. , WALDHERR R. , VEITH S. , CZYGAN P. , WEBER E. , DEUTSCH‐DIESCHER O. G. , KOMMERELL B.
Published: March 2008

Abstract. Gamma‐glutamyltransferase activity was determined in duodenal biopsies, and in the sera of forty‐six non‐alcoholic and eighteen alcoholic patients with a daily alcohol consumption of more than 80 g. Additionally, duodenal morphology was examined in biopsy material obtained at the same time. In both alcoholics (P < 0·05) and in non‐alcoholics (P < 0·001) the duodenal gamma‐glutamyltransferase activity revealed a significant positive correlation with duodenal villus length. In addition, alcoholics exhibited a significant decrease in duodenal villus length (338 ± 13 vs. 363 ± 13 μm, P < 0·01), and a significant increase in duodenal gamma‐glutamyltransferase activity (13·0 ± 1·4 vs. 8·4 ± 0·6 mU mg‐1 protein, P < 0·01) when compared to controls. No significant correlation was found between duodenal and serum gamma‐glutamyltransferase activity in alcoholics and non‐alcoholics. During follow up of two patients, duodenal gamma‐glutamyltransferase activity decreased and duodenal villus length increased after withdrawing alcohol. These data underline the damaging effect of alcohol on the duodenal mucosa and demonstrate that chronic alcohol intake reversibly effects duodenal gamma‐glutamyltransferase. In addition, the small intestine appears of minor importance as an origin for the elevated serum gamma‐glutamyltransferase activities seen in the alcoholic.
Lipolytic and anticoagulant activities of a low molecular weight fragment of heparin
Authors: PERSSON E. , NORDENSTRÖM J. , NILSSON‐EHLE P. , HAGENFELDT L.
Published: March 2008

Abstract.Low molecular weight heparin (LMWH) and standard heparin were given intravenously to six healthy subjects receiving a continuous infusion of Intralipid®. After infusion, antifactor Xa, antithrombin III and coagulation activity (Normotest) were the same for both heparins. Activated partial thromboplastin time increased significantly, but the increase was much higher after standard heparin (+473%) than after LMWH (+48%). The increase in lipoprotein lipase activity was less pronounced after LMWH infusion. This resulted in a smaller decrease in Intralipid‐triglyceride concentration and a smaller increase in both plasma FFA concentration and Intralipid fractional removal rate compared to standard heparin.

This study shows that the plasma lipolytic potential of LMWH is weaker than that of standard heparin when given in doses with equipotent anticoagulation. LMWH may therefore be preferable to standard heparin as an antithrombotic agent in clinical situations where a high plasma lipolytic activity may be disadvantageous.
Role of gastrointestinal tract and liver in acetate metabolism in rat and man
Authors: HERRMANN D. B. J. , HERZ R. , FRÖHLICH J.
Published: March 2008

Abstract. Net acetate uptake/release by various tissues was studied in vivo in fed, starved and Paromomycin‐treated rats and in patients with cirrhosis of the liver. In humans the portal vein, hepatic vein and hepatic arterial blood flow rates were determined simultaneously. In rats acetate is only intestinally produced and released into the portal vein. Intestinal production is decreased by 33% in starved and Paromomycin‐treated rats compared to fed animals. Portal vein‐hepatic vein acetate differences are linearly related to the portal vein acetate concentration (r= 0·92). Acetate uptake from the portal vein by the liver was found when the portal venous concentration exceeded 180 μmol 1‐1. In humans the hepatic net acetate uptake from the portal vein/net acetate release into the hepatic vein, measured as μmol min‐1, is linearly related to the portal vein acetate concentration (r=0·97). Furthermore, portal vein‐hepatic vein differences are correlated to the arterial concentration (r=0·96). The data indicate that the liver may homeostatically regulate the systemic acetate concentration in rat and man.
Cytotoxicity of lectins on rat intestinal mucosa enhanced by neuraminidase
Authors: LORENZ‐MEYER H. , ROTH H. , ELSASSER P. , HAHN U.
Published: March 2008

Abstract. The lectins wheat germ agglutinin (WGA) and Concanavalin A (ConA) were perfused into an isolated small intestinal segment alone or after prior perfusion with neuraminidase for a 10 day period in the rat. Intestinal morphometry, intraepithelial lymphocyte (IEL) and round cell content as well as digestive capacity was measured in the loop and in the adjacent segments. Both lectins induce a mucosal transformation in all segments but ConA is more effective than WGA. Pre‐incubation with neuraminidase enhances the action of ConA throughout, whereas only a partial enhancement of the effect of WGA is observed. The mucosal transformation after long term perfusion with the lectins resembles the hyperregenerative adaptation of the mucosa due to gluten in coeliac disease and may thus serve as an animal model for this disease.
Serum β2‐microglobulin at remission and relapse in patients with multiple myeloma
Authors: BRENNING G. , WIBELL L. , BERGSTRÖM R.
Published: March 2008

Abstract. Serum β2‐microglobulin (S‐β2m) was determined before treatment in fifty patients with multiple myeloma (MM), twenty‐two of which had pure Bence Jones (BJ) myeloma. S‐β2m was related to clinical stage before, but not after, a correction of S‐β2m values for co‐existent raised S‐creatinine values (> 106 μmol 1‐1)‐ However, S‐β2m as well as corrected β2m was a parameter of prognostic value. The median expected survival time was 14 months at S‐β2m values > 8·0 mg 1‐1 and 56 months at values<3·5 mg 1‐1. A response to treatment was associated with a decrease of S‐β2m and a stationary course with unchanged values, whereas a relapse or progressive disease was connected with an increase. In β2m producers', i.e. patients with a clear initial high S‐β2m, serial determinations are of value for monitoring patients with MM. In particular, this is the case in BJ myelomas, as they lack a quantifiable serum M‐component. With respect to β2m no difference was found between BJ and other patients with MM.
Blood to interstitial fluid volume ratio in chronic hypokalaemic states
Authors: BOER P. , KOOMANS H. A. , HENÉ R. J. , GEYSKES G. G. , SHAIK B. A. M. VAN , ROOS J. C. , MEES E. J. DORHOUT
Published: March 2008

Abstract. The distribution of extracellular fluid over the intra‐ and extravascular spaces was determined in hypokalaemic and normokalaemic patients. In six patients with Bartter's syndrome, four with pseudo‐Bartter's syndrome, and twenty with essential hypertension (EH) chronically treated with chlorthalidone, serum potassium (serum K+) and extracellular fluid volume (ECFV) were decreased, while plasma volume (PV) and blood volume (BV) were normal (see Table 1 for means, standard deviations, and levels of significance). Consequently, the ratio of BV to interstitial fluid volume (IFV) was increased. In ten patients with EH on long‐term combined enalapril/chlorthalidone therapy, eight EH patients on long‐term spironolactone treatment, and twenty‐three EH patients treated by short‐term sodium restriction, PV, BV, and ECFV were decreased, but serum K+ and BV/IFV were normal. In six patients with primary hyperaldoster‐onism (PHA) serum K+ was decreased, while PV, BV, and BV/IFV were elevated. Significant negative correlations between sK and BV/IFV were found in the Bartter patients (r= ‐0·88) and the pooled data of all patients (r= ‐0·50). These findings suggest an association between chronic hypokalaemia and a fluid shift from the extra‐ into the intravascular space. The hypothesis that this phenomenon is due to a decreased venous resistance as a consequence of chronic hypokalaemia is discussed.
Variant of acute intermittent porphyria with normal erythrocyte uroporphyrinogen‐I‐synthase activity
Authors: MUSTAJOKI P. , TENHUNEN R.
Published: March 2008

Abstract. A kindred in which several members have otherwise typical acute intermittent porphyria but normal erythrocyte uroporphyrinogen‐I‐synthase activity has been described from Finland. We studied two porphyric members of this kindred, two patients with typical acute intermittent porphyria, and two healthy controls using the δ‐aminolaevulinic acid loading test and by measuring the erythrocyte enzymes of haem biosynthesis. The excretion pattern of haem precursors after the δ‐aminolaevulinic loading test in the members of the kindred studied, was similar to that in typical acute intermittent porphyria suggesting an identical enzyme defect in the liver. The activity of all red cell enzymes studied was normal in the members of the kindred. The results suggest that porphyria in the kindred studied is a variant of acute intermittent porphyria, where the uroporphyrinogen‐I‐synthase defect is manifested in the liver but not in red cells.
Changes in quantitative measures of hepatic function after 90% hepatectomy in rats
Authors: POULSEN H. E. , GAUB J. , IVERSEN J.
Published: March 2008

Abstract. Quantitative measures of liver functions were investigated in rats up to 360 h after 90% hepatectomy and related to total hepatic DNA. Galactose elimination capacity (cytosolic phosphorylation of carbohydrate), p‐nitro‐anisole demethylase activity (endoplasmic drug hydroxylation) and prothrombin index (protein synthesis at rough endoplasmic membranes) were initially reduced as much as the liver weight, but recovered differently. During hepatic regeneration prothrombin index and galactose elimination were back to control values after an interval of 360 h, while p‐nitro‐anisole demethylase activity was about 0·4 times control value after that interval. The correlation between total hepatic DNA and liver weight, and between total hepatic protein and liver weight was 0·92 in both cases, indicating their close relationship during hepatic regeneration. Compared to earlier studies on 70% hepatectomy the recovery of metabolic functions after 90% hepatectomy is delayed, as compared to regeneration of total hepatic DNA. The compensatory hyperfunction observed after 70% hepatectomy was not found after 90% hepatectomy, indicating a lost ability to hyperfunction when hepatic function is reduced close to the minimal residual function. This is suggested to be important for the sudden onset of hepatic insufficiency.
Thigh muscle mass and function in patients treated with glucocorticoids
Authors: HORBER F. F. , SCHEIDEGGER J. R. , GRÜNIG B. E. , FREY F. J.
Published: March 2008

Abstract. Treatment with glucocorticoids causes wasting of proximal skeletal muscles. There is evidence that physical training improves muscle mass and strength in glucocorticoid‐treated rats. Whether this is also true in humans is unknown. The present investigation was designed to establish in what respect moderate physical training may alter muscle mass and function as assessed quantitatively by computed tomography (CT) and with an isokinetic dynamometer (Cybex® II). Compared with matched controls, both female (n= 17) and male (n= 22) patients treated with prednisone (15±4 ± 6±6 mg die‐1) had a lower mid‐thigh muscle area of 20 and 45% and an increased mid‐thigh fat/muscle ratio of 25 and 100%, respectively. The mean peak torque and the total work output of the thigh muscle were lower by 20–30% (n= 14). Fifty days of isokinetic training in six patients increased the thigh muscle area, decreased the thigh fat area and normalized the mean peak torque and total work output. Thus, glucocorticoid‐induced muscle wasting can be reversed by increasing physical activity.
Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha2 adrenoceptors properties
Authors: BERLAN MICHEL , LAFONTAN MAX
Published: March 2008

Abstract. Investigations were carried out to demonstrate the function and the possible advantage of the interplay between β1 and α2 adrenoceptor sites in the regulation of human subcutaneous fat‐cell lipolysis. α2 and β adrenoceptor binding studies were conducted with antagonist radioligands and revealed that α2‐adrenoceptors ([3H] yohimbine and [3H] rauwolscine binding sites) are more numerous than β1‐adrenoceptors ([3H] dihydroalprenolol and [3H]CGP‐12177 binding sites) in human fat‐cell membranes. Physiological agonists epinephrine and norepinephrine competed with [3H]‐ligand sites with a higher affinity for α2 sites than for β1 sites. Epinephrine exhibited a higher affinity than norepinephrine for the α2 sites; the two amines had the same affinity for β1 sites. In lipolysis studies conducted in the absence of adenosine deaminase the β lipolytic action of the biological amines predominated; after α2‐adrenoceptor blockade by yohimbine or idazoxan, the amines exhibited an intrinsic activity similar to that of isoproterenol. When adenosine was prevented from accumulating in the incubation medium by inclusion of adenosine deaminase, low concentrations of epinephrine and norepinephrine preferentially exerted an antilipolytic action. We conclude that: (i) the lipolytic response in abdominal human subcutaneous fat cells to physiological amines results from the interplay between β1‐ and α2‐adrenoceptor stimulation; (ii) α2‐ adrenoceptors, with their higher number and higher affinity for the physiological amines, and the adrenoceptor population involved at the lowest (i.e. physiological) concentrations of the amines; and (iii) the β1 sites with a lower number and weaker affinity for epinephrine and norepinephrine are involved when higher concentrations of the amines reach the plasma membrane. Thus, α2 adrenoceptors appear to be hormonal extrasynaptic receptors which control the state of activity of the human fat cell.
Direct determination of leucine metabolism and protein breakdown in humans using L‐[1‐13C, 15N]‐leucine and the forearm model
Authors: CHENG K. N. , DWORZAK F. , FORD G. C. , RENNIE M. J. , HALLIDAY D.
Published: March 2008

Abstract. We have used the forearm model to study protein metabolism in six normal healthy subjects in the fed state using L‐[1 –13C, 15N]‐leucine as the substrate tracer.

Deep venous and arterialized venous blood samples from the forearm were collected at 10‐min intervals 2±5 h into a primed‐continuous infusion of the dilabelled tracer. Arterialized venous blood was obtained using a ‘hot‐box’ technique and forearm blood flow was measured by mercury strain‐gauge plethysmography.

The concentration and isotope enrichment of leucine and its metabolites, α‐ketoisocaproic acid and CO2, in deep venous and arterialized venous blood were measured by gas chromatography‐mass spectrometry and isotope ratio‐mass spectrometry.

The rates of leucine deamination and reamination were 388 ± 24 (mean ± SEM) and 330 ± 23 nmol (100 ml)‐1 min‐1 respectively, whilst protein synthesis and breakdown rates were 127 ± 11 and 87 ± 10 nmol (100 ml)‐1 min‐1 respectively across the forearm in the fed state. We have demonstrated that the use of doubly labelled leucine as tracer and application of the mathematical model developed in this study, permits the comprehensive quantification of leucine kinetics including protein breakdown.
Renal water and sodium handling in compensated liver cirrhosis: mechanism of the impaired natriuresis after saline loading
Authors: CAREGARO L. , LAURO S. , ANGELI P. , MERKEL C. , GATTA A.
Published: March 2008

Abstract. The present study was attempted to evaluate sodium and water balance in compensated liver cirrhosis. Renal sodium and water handling was studied in six cirrhotic patients without ascites and/or oedema and in six controls before and after saline loading. Fractional sodium reabsorption at the various nephron sites (proximal, diluting and distal) was evaluated by means of clearance techniques during maximal water diuresis and hypotonic saline infusion. Compensated cirrhotic patients showed a normal baseline sodium and water balance but a blunted natriuretic response when saline loaded (urinary sodium excretion after saline load = 338 ± 290 compared to 933 ± 504 μmol min‐1 of controls; P<0±05). The impaired natriuresis was found to be related to an increased reabsorption of sodium in the proximal tubule (proximal fractional sodium reabsorption = 88±4 ± 3±8 compared to 81±7 ± 4±3% of controls; P<0±05). These findings confirm the hypothesis that renal sodium handling abnormalities might precede ascites formation. Additional studies, however, are necessary to further define renal factors mediating the increased reabsorption of sodium in compensated liver cirrhosis.
Total and unbound Cortisol‐, progesterone‐, oestrone‐ and transcortin‐binding activities in sera from patients with myocardial infarction: evidence for differential responses of good and bad prognostic cases
Authors: ZOUAGHI HASSEN , SAVU LIA , GUEROT CLAUDE , GRYMAN RAYMOND , COULON ALINE , NUNEZ EMMANUEL A.
Published: March 2008

Abstract. Day‐of‐admission sera from myocardial infarction patients (MI) and patients with cardiopathies other than MI (non‐MI) were analysed for total and unbound Cortisol (F), progesterone (P4), oestrone (E1), and corticosteroid binding activities (CBG).

The MI who survived (n= 28) showed high increases of F, P4 and E1 compared to healthy controls. By contrast, the MI who died within 10 days of admission (n= 6) had unchanged F and less increased P4 and E1 than survivors. The non‐MI (n= 6) had higher F and E1 than controls but normal P4.

The unbound steroids were increased in all patients: however, the MI who died showed much smaller rises than survivors (P< 0±001 for unbound F and E1 increases in survivors vs. deceased).

The CBG activity was in all MI lower than in normals (P<0±001) but unchanged in non‐MI.

These results are discussed in terms of the potential significance of unbound plasma steroids as predictors of MI severity.