摘要:

Abstract.To evaluate indicators of inflammatory changes in the airways of young smokers we have measured the levels of several eicosanoids in bronchoalveolar lavage (BAL) fluid of 18 female smokers (age 33 ±2 years) and 9 female non‐smokers (age 29 ± 2 years) who were hospitalized for treatment not related to any pulmonary disease. In each BAL specimen the following eicosanoids were determined by radioimmunoassay: prostaglandin (PG) E2; PGF2x; 9α, 1 lβ‐PGF2, a metabolite of PGD2; 6‐keto PGF1x, a metabolite of prostacyclin; thromboxane (Tx) B2, a metabolite of TxA2; the 5‐lipoxygenase products 5‐hydroxy‐eicosa‐tetraenoic acid (HETE), leukotriene (LT) B4and LTC4; the 12‐lipoxygenase product 12‐HETE; and the 15‐lipoxygenase product 15‐HETE. The concentrations of the cyclooxygenase products (pg ml‐1) in the BAL fluid of the non‐smokers were: PGE215.4±1.9, PGF2x, 7.6±1.0, 9α,11β‐PGF28.7±1.8, TxB28.8 ± 1.3, and 6‐keto PGF1αonly 1.5±0.8. The concentration of the lipoxygenase products were: 15‐HETE 781 ± 200,12‐HETE 193 ± 33,5‐HETE 14.0 ± 3.1, LTC49.5±3.1, LTB46.2± 1.4. BAL fluid from smokers contained two‐ to three‐fold higher levels of TxB2and PGF2α(P<0.05). The levels of TxB2and PGF2αwere positively correlated to the number of package years (rs= 0.55 andrs= 0.65,P<0.02). The concentrations of 5‐, 12‐ and 15‐HETE tended to be higher in BAL fluid from smokers, but this was not significant. We conclude that in BAL fluid from females who denied pulmonary symptoms, the concentration of 12‐ and 15‐lipoxygenase products is 15 — 100‐fold higher than that of 5‐lipoxygenase or cyclooxygenase products. In these subjects smoking is associated with higher concentrations of bronchoconstrictive cyclooxygenase products and a tendency towards higher levels of 5‐, 12‐ and 15‐HETE, probably reflecting inflammatory changes in the airways. Therefore, these results indicate that smoking induces formation of the metabolites that may play a role in the development of chronic airways obstruction especially when inf

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01466.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.A novel method based on mathematical analysis of the dose‐response curve obtained by radioimmunoassay was used to determine anti‐HBs affinity and concentration in 29 healthy subjects vaccinated with plasma‐derived hepatitis B vaccine. Anti‐HBs affinity as well as its serum concentration increased with time in most vaccine recipients; however, the pattern of affinity maturation varied widely between individual subjects. In 20 subjects the highest increase in antibody affinity was observed after the third dose of vaccine, whereas in nine cases values of affinity remained low and relatively constant throughout the time of th

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01467.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Insoluble immunoglobulin aggregates present in the synovial fluid of patients with rheumatoid arthritis have been examined for their ability to activate reactive oxidant and granule enzyme secretion from bloodstream neutrophils. These insoluble complexes activated luminol chemiluminescence, but did not activate O2‐, H2O2or granule enzyme secretion and did not activate lucigenin chemiluminescence, which also measures reactive oxidant secretion. Hence, the luminol chemiluminescence detected after activation by insoluble immunoglobulin aggregates must be due to intracellularly generated reactive oxidants, i.e. produced within phagolysosomes. Because reactive oxidant and granule enzyme secretion has occurred within rheumatoid joints, other mechanisms of neutro‐phil activation must ex

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01468.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Urodilatin (ANF(95–126)), an analogue of the atrial natriuretic factor (ANF(99–126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1±0.8 years; X ± SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 μg kg‐1body weight (bw) (n= 6 per dosage group). Urodilatin dose‐dependently increased heart rate and cardiac index. A dose‐dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriur‐esis increased 7‐fold, 5‐fold and 4‐fold, respectively. Renal effects were not different between dosage groups.Compared with ANF(99–126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 μg kg‐1,n= 6; ANF ‐1.8 ± 0.5, URO: ‐5.5±1.1 mmHg,P<0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99–126) produced only a transient decrease of PAP. Similarily the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3±1.2 to 3.8±0.9 mmHg (P<0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficia

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01469.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.In hypercholesterolemia significant changes in the nucleotide pattern of erythrocytes and lymphocytes as determined by high performance liquid chromatography were found. The decrease in ATP of lymphocytes in hypercholesterolemia from 10.4 ± 0.3 to 7.0 ± 0.4 nmol mg‐1protein (n= 8) was associated with an increase in ADP from 2.2 ±0.2 to 4.0 ±0.2 nmol mg‐1protein (P<0.005). The pattern of guano. sine phosphates likewise was found to be changed in hypercholesterolemia. Akin to lymphocytes, red blood cells displayed marked changes in nucleotide levels. No such changes were observed in platelets. Cultured lymphocytes incubated with human plasma low density lipoproteins (LDL) (140 mg cholesterol dl‐1) displayed a reversible fall in ATP and an increase in ADP by about 40% and 160%, respectively, with high density lipoproteins (HDL) or very low density lipoproteins (VLDL) being essentially ineffectual. It is concluded that in hypercholesterolemia a significant change in the nucleotide pattern of blood cells is exerted by the increase in LDL. Possible pathophysio‐logical implications ar

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01470.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxy‐terminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow‐up (n= 9), one minimum and two maxima were found for S‐PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S‐PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow‐up result/pre‐operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1‐day minimum of S‐PICP was 0.60 (SD 0.18), and that of S‐PIIINP 0.89 (0.27), (P<0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7‐day peak of S‐PICP was 1.4 (0.5), and that of S‐PIIINP 2.5 (1.2), (P<0.0001, CI 0.81 to 1.42). The 2‐month‐peak of S‐PICP was 1.6 (0.3), and at the same time the relative S‐PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n= 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre‐operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S‐PICP (3/8) and S‐PIIINP (5/8). The results demonstrate the ability of extracellular matrix to adjust its turnover in r

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01471.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2–4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apoli‐poproteins were also documented in pre‐ and post‐clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non‐diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 {range 2.3–22.3} in the morning and 9.9 {3.0–22.5} mmol h‐1l‐1in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 {4.4–30.6} to 10.4 {3.3–31.3} mmol h‐1l‐1,P<0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54,P= 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 {9.8–32.7} to 12.6 {6.3–28.3} mmol h‐1l‐1,P<0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1and B. The change in hepatic lipase activity was positively related to fasting apoprotein B and total cholesterol concentration (bothr= 0.72,P= 0.042) and both the fasting LDL cholesterol (r = 0.82,P=0.021) and the change in LDL cholesterol during the clamp study (r = 0.81,P= 0.022). Thus, acute physiological hyperinsulinaemia in normal and type 2 diabetic man causes a decrease in hepatic lipase activity. This may reflect a direct effect of insulin or, alternatively, it may be secondary to insulin‐mediated alt

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01472.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Intrinsic hepatic clearance (K) of indocyanine green (ICG) is used as a quantitative measure of liver function. ICG is tightly bound to plasma proteins. The purpose of this study was to examine the effect of changes of plasma protein concentration on K. in anaesthetized pigs with intact hepatic circulation. In addition, an attempt was made to evaluate the corresponding changes of the unbound intrinsic clearance of ICG. The plasma protein concentration was changed by exchange of plasma with either dextran‐70 or donor pig plasma. Plasma albumin concentration was measured in a peripheral artery and changes of the concentrations of other plasma proteins were assumed to parallel those of albumin. ICG was given as a constant infusion and K was calculated from peripheral artery and hepatic vein concentrations of ICG according to the sinusoidal perfusion model. One experimental series comprised 3 measurement periods: From Period 1 to Period 2 (eight animals) albumin concentration was decreased by 36.6 ± 6.5% (Mean±SD). This was associated with an increase of K of 32.8 ±28.8% (P= 0.004). From Period 2 to 3 (five animals) albumin was increased by 13.2 ± 3.2% and K decreased by 18.5 ± 8.3% (P= 0.03). In the second experimental series (eight animals), albumin concentration was increased by 21.6± 10.3% and K decreased by 20.3± 8.1% (P= 0.001). For both series, changes in albumin concentration were associated with oppositely directed changes of K in 20 out of 21 comparisons (P<0.001). Thus K depends not only on hepatocyte function but also on plasma protein concentration. This finding should affect interpretation of K when used as a liver function test. Changes of the unbound intrinsic clearance of ICG were examined indirectly by means of the K · a product (a: albumin concentration). According to the overall evaluation of the data the unbound intrinsic clearance of ICG was not affected by the changes in plasma protein concentration, but the results were internally inconsistent, apparently due to a time‐dependency of the K · a product. We suggest this to be due to a slow but steady decrease of the ‘background’ K. After correction for the average decrease of K of 0.102% per min our data were in accordance with the hypothesis that the unbound clearance of K was enhanced by the binding p

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01473.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre‐exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscl

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01474.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.We measured forearm bone mineral density (BMD) using single photon absorptiometry (SPA) and bone mineral content (BMC) and BMD of lumbar spine by dual photon absorptiometry (DPA). The population consisted of 463 bone healthy subjects, 346 females and 117 males aged 20–85 years. Any underlying bone disease or other diseases known to affect bone mass were excluded by physical examination, thoracic and lumbar radiographs and laboratory screening. Patients with osteoarthritis of lumbar spine were excluded as well as patients taking drugs known to affect bone mass. All bone mass values declined with age. Body height also declined with age by 1.2 cm and 1.8 cm per 10 years (— 0.7% and — 1 %) in females and males respectively. Main effects of age, body height, ‐surface, ‐weight and ‐mass index on bone mass were calculated using multiple regression models. In males and females lumbar BMC measured in gHA depended primarily on body height and secondarily on age. Spinal BMD as measured in g cm‐2was primarily dependent on age and then on height. In females forearm BMD depended primarily on age and then on body surface, in males on body surface only.Using receiver operating characteristic (ROC) analysis the ROC area increased from 0.81–0.85 (n.s.) including body height into spinal BMD values leading to a higher sensitivity of measurements of spinal bone mass in recognizing 58 patients with spinal postmeno‐pausal osteoporosis. Including body surface into forearm BMD measurements ROC area increased from 0.66–0.69 (P=0.055).We conclude from these data that measurements of bone mass not only depend on age and sex, but on body height and surface. These anthropometric parameters and their changes over decades have to be taken into account when examining any effects on bone mass in cross‐sectional studies. Including these parameters into bone mass values may lead to higher sens

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01475.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY