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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 289 records · Page 16Linked to original sources

Lipoproteins in plasma from patients with low LCAT activity due to biliary obstruction.

A high density lipoprotein (HDL) fraction, designated cholestatic HDL1, has been isolated by zonal ultracentrifugation from patients with long-standing biliary obstruction. This lipoprotein fraction consists exclusively of disc-shaped particles rich in phospholipid and unesterified cholesterol. The fatty acid composition of the minor cholesteryl ester fraction was characterized by a low content of linoleic acid. Apoprotein E was the dominating protein' component, while only small amounts of apolipoprotein A-I were found. Immunochemical studies of cholestatic HDL1 indicate that a considerable proportion of the particles contained apo E as its only protein constituent. All patients had a markedly reduced endogenous cholesterol-esterifying ability. The finding of apparently primary LpE particles in biliary obstruction may be related to this secondary LCAT deficiency.

Apoproteins↗

Plasma lipoprotein changes in experimental cholestasis in the dog.

Plasma lipoproteins were compared before and after surgical induction of extrahepatic biliary obstruction in dogs by immunochemical techniques, zonal ultracentrifugation and gel filtration. A considerable increase in LDL was found one week after operation, with a zonal ultracentrifugal pattern which was more complex than that found before operation. The lipid composition was characterized by an increase of phospholipids and a decrease of triglycerides in cholestatic LDL fractions. None of the fractions displayed the inverse cholesterol-cholesterol ester ratio, characteristic for human LP-X. The apoprotein composition of cholestatic LDL was also markedly changed. Apoprotein A I, already present in the normal LDL2 subclass, increased and two apoproteins with apparent molecular weight of 35000-40000 appeared in considerable amounts. The amount of HDL was decreased during cholestasis without any appreciable changes in composition.

Animals↗

Experimental normocalcaemic hyperparathyroidism induced by renal venous congestion.

Ligation of the inferior vena cava above the renal veins in male Sprague-Dawley rats produces a predominantly transient renal injury with vascular congestion, tubular degeneration and necrosis with calcification. This is accompanied by impaired renal function with temporary azotaemia, hyperkalaemia, phosphate retention but with a normal calcium level. The parathyroid glands on the second postoperative day show cellular hypertrophy and on the third and fourth days signs of rapid cell proliferation with numerous mitoses. Thereafter the glands remain enlarged.

Animals↗

Characterization of high density lipoproteins in human cholestasis.

High density lipoproteins (HDL) of plasma from patients with long-standing cholestasis were studied by several methods including crossed immunoelectrophoresis, gel filtration, and zonal ultracentrifugation. The crossed immunoelectrophoretic pattern against anti-HDL was characterized by the presence of several immunoprecipitates, in striking contrast to the pattern formed by normal HDL. One of these precipitates corresponded to a lipoprotein species dominated by apoprotein A-II (apo A-II). Zonal ultracentrifugation of cholestatic plasma showed a decrease of HDL and a disappearance of the normal delineation of HDL2 and HDL3. In addition a new component designated HDL1-C was observed. Consistent results were found at studies of the molecular size distribution of cholestatic HDL by gel filtration on Sephadex G-200. The lipid and apoprotein composition of isolated cholestatic HDL fractions differed considerably from normal. Most notable were the high proportions of phospholipids and free cholesterol and the occurrence of the apoprotein E (arginine-rich protein) in remarkably high amounts especially in the abnormal HDL1-C.

Adult↗

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein.

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.

Adult↗

Zonal ultracentrifugation of plasma lipoproteins from normal and cholestatic pigs.

The plasma lipoproteins in normal and cholestatic pigs were isolated by zonal ultracentrifugation and studied with respect to apoprotein and lipid composition. In contrast with the distribution in human plasma, only one HDL-population but two LDL-populations were demonstrated. No cholestatic lipoprotein similar to the human lipoprotein X was observed. HDL and the lighter LDL component were largely unchanged in cholestasis. The immunochemical properties were changed to some extent. Thus HDL-reacting material was found in the heavier LDL-component and VLDL after cholestasis but not before.

Alanine Transaminase↗

Effects of apolipoproteins on lipoprotein lipase activity of human adipose tissue.

The effect of apolipoproteins isolated from HDL and VLDL on the activity of lipoprotein lipase (LPL) of adipose tissue was studied. The CII apoprotein was found to activate LPL. This activation was strongly inhibited by CI, AI (apo-Lp-Gln I), and the arginine-rich apoprotein, whereas AII and CIII exhibited a considerably lower inhibitor effect.

Adipose Tissue↗

Peptides with NH2-terminal tryptophan in adrenocorticotrophic hormone and melanocyte-stimulating hormone granules of adenohypophysis.

Fluorescence microscopy has demonstrated formaldehyde-ozone-induced fluorescence in the pars intermedia cells (melanocyte-stimulating hormone cells) and in certain cells of the pars distalis of the mammalian pituitary. From histochemical and chemical evidence the fluorescence is believed to reflect the presence of peptides with NH2-terminal tryptophan. In the pars distalis of hamster, cat and pig pituitary, the cells that exhibit formaldehyde-ozone-induced fluorescence have now been identified as adrenocorticotrophic hormone (ACTH) cells by immunohistochemistry. Granules from pig pituitaries were purified by passage through a succession of Millipore filters followed by centrifugation on a continuous sucrose gradient. Two granular fractions were identified by electron microscopy and found to contain high concentrations of peptides with NH2-terminal tryptophan as well as high ACTH bioactivity. These fractions, when pelleted and analyzed histochemically, displayed formaldehyde-ozone-induced fluorescence and ACTH-like immunoreactivity.

Adrenocorticotropic Hormone↗

Blood glucose measurement with Dextrostix and new reflectance meter.

A new instrument, Eyetone, has been produced for use with a Dextrostix reagent strip for estimating blood sugar levels. It differs from the Dextrostix Reflectance Meter in having only one meter scale, a two-point calibration, and a range of measurement limited to 10-400 mg/100 ml. Results with the manufacturers' original calibration were unsatisfactory, but when recalibrated the performance of the instrument gave a regression equation line close to the ideal. The three Eyetone instruments tested were comparable in their accuracy and functional stability. Packed cell volumes in the blood samples in the range of 30-50% had a negligible effect on the results. The Dextrostix-Eyetone method represents a quick and reliable alternative to conventional laboratory methods for blood sugar estimation. It is especially useful for patients outside hospital.

Blood Glucose↗

Distribution and dilatory effect of vasoactive intestinal polypeptide (VIP) in human cerebral arteries.

Vasoactive intestinal polypeptide (VIP)-containing nerve fibers were demonstrated in human pial arteries by immunocytochemistry. Fine varicose fibers were located in the adventitia close to the media layer. Measurements by radioimmunoassay revealed concentrations of VIP between 0.7 and 2.7 pmol/g in the major arteries at the base of the brain, obtained at autopsy. Isolated human pial arteries, obtained in conjunction with neurosurgery, relaxed in a concentration-dependent manner upon administration of VIP. The relaxation of the vessels amounted to 57 +/- 9% of the contraction elicited by prostaglandin F2 alpha (2.5 microM) with an EC50 value of (8.5 +/- 1.2) X 10(-9) M.

Cerebral Arteries↗

Delta sleep-inducing peptide (DSIP)-like immunoreactivity in gut: coexistence with known peptide hormones.

Delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) has previously been demonstrated in brain neurons and in endocrine cells of the pituitary and the adrenal medulla. By means of three different antisera against synthetic DSIP we now describe the occurrence and distribution of DSIP-LI in several gut endocrine cells. The human gut was the richest source, where DSIP-LI was located in gastrin/CCK, secretin and PYY/glicentin cells. The rat and pig gut harbour a moderate number of immunoreactive cells in the antral mucosa but in the intestines DSIP-LI-containing cells were very few. By radioimmunoassay, the concentration of DSIP-LI was determined in extracts of various gut regions from man, pig and rat. The highest concentrations were found in all human specimens compared with corresponding samples in the pig and rat. In all three species, high-performance liquid chromatography revealed a single peak of DSIP-like material with approximately the same retention time as DSIP 3-9. Taken together, the present results provide evidence for the presence of DSIP-LI in gut endocrine cells in man, pig and rat; the human gut seems to be the richest source of DSIP-like peptides.

Adult↗

Hydra head activator-like immunoreactivity in human brain astrocytomas grade III-IV and the surrounding brain tissue.

We have developed a specific and sensitive radioimmunoassay for the hydra head activator neuropeptide (HHAP). The antibody recognizes the C-terminal portion of HHAP and shows no cross-reactivity with other neuropeptides. The assay allows measurement of HHAP-like material in tissue extracts with a minimum detectable concentration of 22 fmol/ml standard HHAP (2 fmol/tube). The concentration of immunoreactive (IR) HHAP in histopathologically characterized tissues was determined in 43 specimens from astrocytomas grade III-IV and surrounding brain tissue from 18 patients. Twenty-two control specimens of gray and white matter and five from hypothalamus were taken from 5 brains at autopsy. The concentration of IR-HHAP in the brain tumors, including the actively growing tumor front, is lower than in normal brain, and thus appears not to act as a growth factor. High performance liquid chromatography (HPLC) of extracts of hypothalamus and tumors revealed two major peaks of IR-HHAP; one eluted with the same elution volume as synthetic HHAP. HPLC of cerebral cortex extracts revealed only one major peak of IR-HHAP eluting close to the void volume, which may indicate a posttranslational processing variability of HHAP in different brain regions. By immunocytochemistry HHAP immunoreactivity was localized to the cytoplasma of neuroectodermal cells.

Amino Acid Sequence↗

Amidated joining peptide in the human pituitary, gut, adrenal gland and bronchial carcinoids. Immunocytochemical and immunochemical evidence.

The distribution of the proopiomelanocortin-derivated amidated joining peptide (JP-N) was examined in the human pituitary gland, adrenal gland, gut and in three bronchial carcinoids. Double immunostaining showed coexistence of immunoreactive JP-N and other proopiomelanocortin derivatives, e.g., ACTH, beta-endorphin, Pro-tau-MSH, in the pituitary gland and adrenal medulla. The JP-N immunoreactive cells in the adrenal medulla were identified as a subpopulation of adrenaline-producing cells by means of an antiserum against phenylethanolamine N-methyltransferase. In the gut immunoreactive JP-N was costored with somatostatin in endocrine cells. Using radioimmunoassay, JP-N was found in higher concentrations than ACTH and alpha-MSH in the gut but not in the adrenal gland. Gel chromatography of gastric antrum and adrenal gland extracts showed three and two dominating components of immunoreactive JP-N, respectively, but under reduced conditions most of the immunoreactive material appeared as of low molecular weight in both extracts. In conclusion, immunoreactive JP-N is a major product from the processing of proopiomelanocortin in human extrapituitary tissues. The molecular forms of immunoreactive JP-N correspond to previous findings in the human pituitary gland.

Adrenal Glands↗

Neuropeptides in guinea pig trachea: distribution and evidence for the release of CGRP into tracheal lumen.

The airways of the guinea pig are richly innervated by peptide-containing nerve fibers. Among the most abundant neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are stored in nerve fibers located predominantly within and beneath the epithelium, and vasoactive intestinal peptide (VIP), which is located in fibers running mainly among smooth muscle bundles and seromucous glands. Sensory denervation (capsaicin treatment) of adult guinea pigs caused an almost total disappearance of CGRP- and SP-containing nerve fibers, while the density of VIP-containing nerve fibers located in smooth muscle seemed to increase. In the isolated trachea, perfused luminally, CGRP was found to appear in the intraluminal fluid after exposure to capsaicin but not after electrical vagal stimulation. CGRP concentrations in the tracheal wall did not change significantly. Luminally applied CGRP did not affect smooth muscle tension, measured as intraluminal volume changes.

Animals↗

Human pheochromocytoma cells studied in culture contain large amounts of DSIP-like material.

Delta sleep-inducing peptide (DSIP)-like immunoreactive (LI) material has been detected in nine different human pheochromocytoma tumors by immunocytochemistry. In primary tumors subjected to indirect immunofluorescence a variable number of tumor cells (25-75%) showed positive cytoplasmic labeling after incubation with DSIP antiserum. Tumor cells grown in culture were strongly labeled by the DSIP antiserum with DSIP-LI concentrated to cell bodies. Electron microscopic immunocytochemistry (immunogold labeling) of pheochromocytoma cells demonstrated DSIP-LI over the dense core of secretory granules. The presence of DSIP-LI in several HPLC fractions from conditioned culture media indicates secretion of DSIP-LI from cultured pheochromocytoma cells. The observations suggest that DSIP-LI is synthesized and stored in secretory granules before release. The different HPLC profiles from each of the tumors may reflect differences in processing or turnover of DSIP-LI in pheochromocytoma cells.

Adrenal Gland Neoplasms↗