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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 235 records · Page 13Linked to original sources
PubMed1995

Effect of oxidizing agents and haemin on the phosphorylation of eukaryotic elongation factor 2 in rabbit reticulocyte lysates.

Incubation of rabbit reticulocyte lysates in the absence of added haemin resulted in the phosphorylation of a 95 kDa protein. This protein was suggested to be elongation factor 2 (eEF-2) based on the following observations, (i) phosphorylation of the 95 kDa protein was Ca2+ and CaM-dependent. (ii) eEF-2 supplemented to the lysates became phosphorylated and co-migrated with the endogenous 95 kDa phosphoprotein upon electrophoresis in SDS gels. (iii) The tryptophane specific cleavage pattern obtained from the isolated 95 kDa phosphoprotein was identical to that of phosphorylated eEF-2. Phosphorylation of the 95 kDa protein was stimulated by oxidizing agents such as oxidized glutathione and NAD+ and inhibited by addition of haemin. The haemin concentration needed for 50% inhibition (IC50) was 2.5 microM. Haemin also had an inhibitory effect on eEF-2 phosphorylation in a system containing highly purified components (IC50 = 2 microM). In this system haemin inhibited phosphorylation of eEF-2 even in the presence of a 100-fold excess of beta-mercaptoethanol. Oxidizing agents had no effect on the kinase activity in the purified system.

Animals↗
PubMed1995

Glycosylated peptide hormones: pharmacological properties and conformational studies of analogues of [1-desamino,8-D-arginine]vasopressin.

Two analogues of the antidiuretic drug [1-desamino,8-D-arginine]vasopressin (DDAVP), which have a glycosylated serine at position 4, have been prepared by Fmoc solid phase peptide synthesis. The glycosylated analogues had significantly higher bioavailabilities than the nonglycosylated [D-Tyr2,Ser4]DDAVP and DDAVP on intraintestinal administration in rat. The improved bioavailability resulted from an increased absorption from the small intestine and most likely from an increased stability toward enzymatic degradation, whereas plasma clearance was either unaffected or slightly increased by the glycosylation. The glycosylated analogues displayed only very low agonistic and antagonistic activities at the vasopressin V2-receptor. Conformational studies performed by 1H NMR spectroscopy did not reveal any major influence from glycosylation on the conformation of the peptide backbone. The lack of receptor binding displayed by the analogues is therefore most likely explained by steric repulsion between the carbohydrate moiety and the vasopressin receptor which prevents receptor binding.

Amino Acid Sequence↗
PubMed1995

Flow-cytometric identification and follow-up of mice exposed to x-irradiation: evaluation of a model system.

An experimental model system is presented that allows the identification and follow-up of mice exposed to ionizing radiation using flow-cytometric measurements of peripheral blood cells. In an experiment, properties of peripheral blood cells were analysed with flow cytometry for a rapid identification of individuals exposed to radiation. Individuals were then followed longitudinally in an attempt to identify those developing neoplasias. Male CBA mice, 25 days old, were subjected to fractionated x-irradiation (4 x 1.31 Gy) to induce haematopoietic malignancies. By repeated blood sampling followed by flow cytometry, frequencies of micronucleated erythrocytes and of proliferating nucleated cells were determined. Neoplasias were diagnosed by histopathology. Five days after the end of radiation exposure, increased frequencies of proliferating cells, polychromatic erythrocytes and micronucleated normochromatic erythrocytes clearly distinguished the exposed group from the control group. Increased cell proliferation in peripheral blood cells could be used to identify animals with manifest tumours, although these animals were at a late stage of tumour development. Animals with thymic lymphoma (not generalized) could not be identified with the flow-cytometric parameters used. We consider that this model system has a potential use when a small number of risk individuals need to be identified and monitored within a large population.

Animals↗
PubMed1995

High consumption of fatty fish from the Baltic Sea is associated with changes in human lymphocyte subset levels.

Fatty fish from the Baltic Sea accumulate immunotoxic persistent organochlorine compounds. In a previous study we found inverse correlations between such fish consumption and natural killer (NK) cell levels in a Swedish population. The present study concerns 68 Latvian subjects with high, low or intermediate fish consumption. High fish consumption correlated positively with B cell levels and CD4+/CD8+ ratios, but negatively with levels of cytotoxic (CD8+) T cells. Furthermore, NK cell levels correlated inversely with plasma selenium, one of several strong correlates with fish intake. A high fish diet includes a set of possible immunomodulating agents. It is presently not possible to pinpoint the cause for the observed subset deviations or to establish their possible biological importance.

Adult↗
PubMed1995

Mortality in recurrent mood disorders during periods on and off lithium. A complete population study in 362 patients.

Recent studies have suggested that long-term lithium treatment reduces the high mortality rates of recurrent mood disorders in patients selected for and compliant with treatment at specialized lithium clinics. Whether lithium also generally reduces mortality in this diagnostic category under less select treatment conditions is a question of vital public health interest. The impact of prophylactic lithium on mortality was studied in a complete population of 362 unselected patients with DSM-III-R diagnoses of mood disorders or schizoaffective disorder, hospitalized at least once between 1970 and 1977 and treated with lithium for a minimum of one year. The patients were followed until 1991 or until date of death. The final analyses included 3911 patient years with lithium and, because of temporary or permanent discontinuations, 1274 patient years without lithium prophylaxis. A total of 129 deaths were recorded, compared with the 60.7 deaths that would normally be expected in the general population, yielding a Standard Mortality Ratio (SMR) of 2.1, significantly different from 1.0 (p < 0.001, 95% confidence limits 1.8-2.5). The relative risk of death was 1.7 times higher (p < 0.01, 95% confidence limits 1.2-2.6) during periods off lithium than during periods on lithium. The relative risk of suicide was 4.8 times higher off lithium than on lithium (p < 0.02, 95% confidence limits 1.1-12.6). Suicide, pneumonia, pyelonephritis, and, unexpectedly, pulmonary embolism contributed to the excess mortality both on and off lithium.(ABSTRACT TRUNCATED AT 250 WORDS)

Affective Disorders, Psychotic↗
PubMed1995

Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity.

Thirteen patients (median age, 20 years) with life-threatening primary septic shock (10 meningococcal, 3 pneumococcal infections) were studied prospectively. All had a short history of sepsis (< or = 24 h) and no severe underlying disease. Two (15%) died. The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively). The plasma levels of endotoxin, TNF-alpha, IL-1 beta, and PAI-1 decreased toward normal levels within the first 24 h of treatment, but IL-6 and IL-1ra levels remained high until clinical recovery. On admission, the molar excess of IL-1ra to IL-1 beta was > 2000-fold in 11 of the 13 patients. Acute plasmapheresis in 11 of the 13 patients significantly increased the plasma clearance of TNF-alpha (P = .02).

Adolescent↗
PubMed1995

Neuropsychological assessment of schizophrenic patients during a psychotic episode: persistent cognitive deficit?

Neuropsychological test performance and clinical symptoms were assessed in 14 schizophrenic patients at admission to and discharge from an acute inpatient psychiatric service. Despite significant clinical improvement at discharge, no major change in cognitive performance was observed. Furthermore, patients at discharge were significantly impaired compared with normal control subjects case-matched for gender, age, handedness and level of education. The results suggest that some degree of cognitive impairment may be relatively independent from schizophrenic symptoms and that such impairment may represent part of a residual enduring "trait" vulnerability.

Adult↗
PubMed1995

Differentiation between patients with schizophrenia and borderline disorders in the Percept-genetic Object-Relation Test, PORT.

Schizophrenics (12 males), borderline patients (12 males), and self-selected normal controls (11 males, 17 females) were compared using PORT (Percept-genetic Object-Relation Test), a projective test, diagnosis being on the basis of DSM-III and Kernberg's six descriptive borderline criteria. The aim of the study was to compare the three groups in order to distinguish the two clinical groups from the control group, but also to distinguish the borderlines from the schizophrenic patients with specified diagnosis. The two patient groups differed from the controls on 15 different PORT signs/patterns. In addition, the borderline patients and the three schizophrenics of unspecified diagnosis showed signs in PORT of dissolution anxiety, splitting, whole configuration (fusion) and sexualization as defence, which the schizophrenics with specified diagnosis did not, although catatonic/hebephrenic, simplex, and paranoid schizophrenics could be distinguished in the test. Characteristic of the schizophrenics was also diffusion of domains of object relationships. In a blind prediction study with PORT involving five male and five female patients with severe psychiatric disorders (diagnosed by DSM-III-R), borderline patients could also be distinguished satisfactorily from schizophrenics.

Adult↗
PubMed1995

Uptake and interconversion of plasma unesterified n-3 polyunsaturated fatty acids by the GI tract of rats.

The origin of the linoleic [18:2(n-6)], arachidonic [20:4(n-6)], and docosahexaenoic acid [22:6(n-3)] of the mucosal phospholipids in the gastrointestinal (GI) tract is not known. This study examines whether stomach, small intestine, and colon take up and desaturate-elongate unesterified polyunsaturated fatty acids (PUFA) from blood. Albumin-bound unesterified alpha-[14C]linolenate [18:3(n-3)] and [3H]eicosapentaenoate [20:5(n-3)] were injected intravenously. After 10 min, 1 h, and 18 h, radioactivity of tissue lipids and the degree of interconversion of the 3H-labeled and 14C-labeled fatty acids were determined. After 10 min, the lipids of the gastrointestinal tract contained 3.6% of the 14C (0.5% in stomach, 2.7% in small intestine, and 0.4% in colon) and 4.9% of the 3H (0.6% in stomach, 3.6% in small intestine, and 0.7% in colon). Both fatty acids were acylated mainly into phospholipids, both in liver and gastrointestinal tract. Although the proportions of radioactivity found in desaturation-elongation products increased with time, 15% of the 14C in the liver, 6% in the stomach, 8% in the small intestine, and 11% in the colon were in 20:5 already after 10 min. A rapid interconversion of 18:3 thus occurred both in the liver and in the gastrointestinal tract. In all tissues examined, interconversion of [3H]20:5 to [3H]22:5 also occurred. Interconversion of unesterified PUFA taken up from blood may be an important source of eicosanoid precursors in the gastrointestinal tract.

Animals↗
PubMed1995

Uptake of radiolabeled and colloidal gold-labeled chyle chylomicrons and chylomicron remnants by rat platelets in vitro.

This study examined the uptake of chyle chylomicrons (CMs) and chylomicron remnants (CMRs) by rat platelets in vitro. CMs and CMRs were doubly labeled with [3H]arachidonate ([3H]-20:4) and [14C]cholesterol and were incubated with platelets for up to 4 hours. A significant uptake (binding and/or internalization) of CMs by the platelets occurred, as indicated by the parallel increase of [3H]20:4 and [14C]cholesterol in platelets with incubation time. Addition of unlabeled CMs, VLDLs, LDLs, and HDLs decreased the uptake of labeled CMs. The competition experiments suggested that there is both a saturable binding and a nonspecific uptake of CMs. During incubation with CMs, the proportion of [3H]20:4 in phospholipids decreased and that in 1,2-x-diacylglycerol increased. The data indicated that a phospholipase C-mediated degradation of phosphatidylcholine and phosphatidylethanolamine occurred, whereas [3H]20:4 in triglyceride and 14C in cholesterol ester did not change. Electron microscopic studies after incubation with colloidal gold-labeled CMs (CM-Au's) demonstrated an accumulation of CM-Au particles in the open canalicular system of the platelets. Some CM-Au particles were localized in cytoplasmic vacuoles that were not stained by ruthenium red. Some CM-Au's or free gold particles were in vacuoles that showed acid phosphatase activity, indicating that some true endocytosis of CM occurred. The uptake of [3H]-20:4- and [14C]cholesterol-labeled CMRs was low compared with the uptake of CMs. After incubation with colloidal gold-labeled CMRs (CMR-Au's), only a few platelets contained CMR-Au in their open canalicular systems, and no CMR-Au particles were seen in the cytoplasm or in acid phosphatase-positive vacuoles. Rat platelets can thus interact with CMs by a process that leads to a sequestration in the open canalicular system and endocytosis and a net degradation of CM phospholipids. The conversion of CMs to CMRs counteracts this interaction.

Animals↗
PubMed1995

Expression of functional growth hormone receptors in cultured human osteoblast-like cells.

Recent clinical studies indicate that GH is important for bone remodeling. Patients with GH deficiency exhibit decreased bone density, and GH substitution increases bone density in these patients. The aim of the present study was to investigate the presence of GH receptors and the effects of GH on cultured human osteoblast-like cells. Primary cultures of human osteoblast-like cells were established from trabecular bone. Northern blot analysis, using a probe recognizing exon 10 of the human GH receptor, revealed a 4.7-kilobase transcript corresponding to the human GH receptor. Cultured osteoblast-like cells expressed, as determined by RNase protection assay, approximately one fourth of the GH receptor messenger RNA levels found in liver. Binding studies using 125I-labeled GH revealed a single class of receptors with approximately 2000 binding sites per cell and an association constant (Ka) of 2.6 x 10(9) M-1. GH stimulation of the cultured cells resulted in increased [3H]thymidine incorporation, suggesting that the GH receptors are functional. In summary, the present study shows that cultured human osteoblast-like cells express functional GH receptors.

Base Sequence↗
PubMed1995

Anti-neutrophil cytoplasmic antibodies in chronic inflammatory bowel disease. Prevalence and diagnostic role.

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA), originally found to be associated with vasculitis, have been reported to be present in chronic inflammatory bowel disease. Most often the ANCA staining pattern is of the perinuclear type (p-ANCA), although nuclear and cytoplasmic stainings are seen. Single studies have shown some of the antibodies to react with lactoferrin or cathepsin G; however, most studies have not been able to determine a main antigenic specificity. We studied the prevalence of ANCA in sera from 155 patients with ulcerative colitis, 128 patients with Crohn's disease, and 51 patients with coeliac disease. The presence of ANCA was correlated to disease activity, extent, and age of onset of the diseases. Furthermore, we tried to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA), using elastase, lactoferrin, myeloperoxidase, proteinase 3, and cathepsin G as antigens. METHODS: The sera were screened for ANCA by indirect immunofluorescence. Anti-nuclear antibodies (ANA) were analysed on HEp2 cells, and ELISA for specific ANCA was performed using the antigens mentioned. RESULTS: Most of the sera with positive immunofluorescence had the p-ANCA type of pattern. Seventy-eight of 155 (50.3%) of the patients with ulcerative colitis were ANCA-positive, compared with 31 of 128 (24.2%) of patients with Crohn's disease (p < 0.001). However, in the subgroup with Crohn's colitis, 16 of 44 (36.4%) were ANCA-positive. Only 4 of 51 patients (7.7%) with coeliac disease showed positive immunofluorescence (p < 0.001 compared with ulcerative colitis). Less than 10% of the samples were positive in the specific ELISA assays; thus other than the most well known granule proteins can be the target for ANCA in ulcerative colitis. CONCLUSION: ANCA occur significantly more often in ulcerative colitis than in Crohn's disease. However, the prevalence of ANCA is rather high in Crohn's colitis. ANCA are thus of limited value in differentiating Crohn's colitis from ulcerative colitis. ANCA found in inflammatory bowel disease are different from those associated with vasculitis. The antigen(s) responsible remain to be determined.

Adult↗
PubMed1995

Fish consumption and exposure to persistent organochlorine compounds, mercury, selenium and methylamines among Swedish fishermen.

OBJECTIVES: This study assessed dietary habits and exposure to selenium, persistent organochlorine compounds, methylmercury, and methylamines among Swedish fishermen. METHODS: Two hundred and fifty randomly selected subjects from a cohort of 2896 fishermen from the Swedish east coast (Baltic Sea) and 8477 fishermen from the west coast (Skagerrak and Kattegatt) were interviewed along with 250 referents. Subgroups of fishermen and referents from different coastal areas were also selected for blood and urine sampling. RESULTS: The interview data showed that fishermen ate almost twice as much fish as the 250 referents from the general population. The blood levels of mercury were twice as high, and the plasma selenium levels were 10-15% higher in the fishermen than in the referents. There was, however, no difference between the fishermen's cohorts with respect to these variables. Fishermen from the east coast ate more fatty fish than fishermen from the west coast, and they also had higher blood levels of persistent organochlorine compounds such as polychlorinated biphenyls and polychlorinated dibenzo p-dioxins and furans (present in fatty fish species in the Baltic Sea) than both the westcoast fishermen and the referents. CONCLUSIONS: A cohort of Swedish eastcoast fishermen might be a suitable study base for epidemiologic studies on the mortality and cancer morbidity associated with dietary exposure to persistent organochlorine compounds.

Animals↗
PubMed1995

Ultrasonography in gallstone ileus: a diagnostic challenge.

OBJECTIVE: To describe our experience with ultrasound diagnosis of gallstone ileus in six cases, and to assess the impact of our findings in the light of published reports. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: Six patients with gallstone ileus. INTERVENTION: Abdominal ultrasound examination. MAIN OUTCOME MEASURES--Correlation with plain abdominal films and with findings at laarotomy. RESULTS: In all six cases ultrasound gave a precise diagnosis of gallstone ileus, together with the exact location of the gallstone, whereas plain films usually indicated only intestinal obstruction of unknown cause. There was not mortality and only one postoperative complication, and all patients were alive and well at the time they were last seen. These results compare well with those of other reported series. CONCLUSION: The high morbidity and mortality of gallstone ileus may be reduced if ultrasonography is used in cases of undiagnosed abdominal pain, particularly in elderly patients with protracted symptoms.

Aged↗
PubMed1995

Hydrolysis of galactolipids by human pancreatic lipolytic enzymes and duodenal contents.

Monogalactosyldiacylglycerols (MGDG), digalactosyldiacylglycerols (DGDG) and sulfoquinovosyldiacylglycerols (SQDG) are major lipids in vegetable food. Their digestion and absorption are unknown. This study examines the hydrolysis of galactolipids in vitro with human duodenal contents, pancreatic juice, and purified human pancreatic lipases. Galactolipids were incubated with human duodenal contents, pancreatic juice, pure pancreatic carboxyl ester lipase (CEL), and colipase-dependent lipase with colipase (Lip-Col). Hydrolysis was estimated as release of free fatty acids and by the use of [3H]galactose or [3H]fatty acid-labeled DGDG. Pancreatic juice and duodenal contents hydrolyzed DGDG to fatty acids, digalactosylmonoacylglycerol (DGMG) and water-soluble galactose-containing compounds. The hydrolysis of DGDG was bile salt-dependent and had a pH optimum at 6.5-7.5. Human pancreatic juice released fatty acids from MGDG, DGDG, and SQDG. Purified CEL hydrolyzed all three substrates; the hydrolysis rate was MGDG > SQDG > DGDG. Pure Lip-Col had activity toward MGDG but had little activity against DGDG. Separation of pancreatic juice by Sephadex G100 gel filtration chromatography revealed two peaks with galactolipase activity that coincided with CEL (molecular mass 100 kD) and lipase (molecular mass 50 kD) peaks. In contrast to pure Lip-Col enzymes of the latter peak were as active against DGDG as against MGDG. Thus, DGDG is hydrolyzed both by CEL and by a pancreatic enzyme(s) with a molecular mass of 40-50 kD to fatty acids and lyso DGDG. MGDG, DGDG, and SQDG are all hydrolyzed by human pancreatic juice. Pure CEL hydrolyzed all three substrates.

Bile Acids and Salts↗
PubMed1995

Simvastatin treatment of hypercholesterolemia in patients with insulin dependent diabetes mellitus.

The effects of 16 weeks therapy with the HMG-CoA reductase inhibitor Simvastatin 10-20 mg (n = 12) was compared to placebo (n = 13) in 25 euthyreoid males with insulin dependent diabetes mellitus and fasting total serum cholesterol above 6 mmol/l. Insulin dependence was defined as a glucagon stimulated C-peptide level less than 0.6 mmol/l. The study was placebo-controlled, double-blind with a parallel group design. Body weight, blood pressure, glycemic control as well as liver enzymes were unchanged and simvastatin was well tolerated by all patients. Ophthalmological slitlamp examination before and at the end of the study period did not show development of new lenticular opacities. Simvastatin decreased serum total cholesterol from 6.7 +/- 1.0 mmol/l (mean +/- SD) to 4.9 +/- 0.4 (p < 0.001 vs. placebo) and LDL-cholesterol from 4.6 +/- 0.7 mmol/l to 2.8 +/- 0.3 (p < 0.001 vs. placebo). HDL-cholesterol and triglycerides remained unaltered. A positive influence on the atherosclerotic process in patients with insulin dependent diabetes mellitus remains, however, to be proven.

Adult↗