Alpha 1-antitrypsin deficiency: lessons learned from the bedside to the gene and back again. Historic perspectives.
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Granulocytes↗
Biomedical subjects
S Eriksson
Publications and source records attributed to S Eriksson.
Medical implications of nosocomial infection with Clostridium difficile.
88 patients above the age of 60 years who contracted Clostridium difficile associated diarrhoea (CDAD) between 1979 and 1986, mostly during their stay in hospital were studied retrospectively as regards nursing time and clinical outcome. These patients were compared with 176 control patients who were matched according to diagnosis on admission to hospital, sex, age and underlying disease. Thromboembolic complications occurred in 14% in CDAD patients (controls 4%) (p = 0.0042). The mortality rate was 21% in CDAD and 7% in controls (p = 0.0009). The median time in hospital for CDAD patients was 50 days (14 days for controls).
Clostridium Infections↗
The use of aqueous two-phase systems to concentrate and purify bovine leukemia virus outer envelope protein gp51.
Enzootic bovine leucosis is a chronic lymphoproliferative disease of cattle. The causative agent, bovine leukemia virus (BLV), is related to the human retroviruses HTLV-I and -II. The external env-protein of BLV, a glycoprotein of 51 kDa, carries neutralizing epitopes and should be an essential component in a vaccine against the virus. Problems have been encountered with the concentration and purification of intact virions of BLV and other retroviruses. During centrifugation procedures the external env-proteins are to a great extent detached and consequently poorly recovered with the virion particles. Therefore, other methods are sought to obtain a high yield of the external glycoproteins. The use of two-phase systems based on water soluble polymers is described for the extraction of BLV-gp51 from culture medium. Several polymer systems were tested and the results showed that some were attractive for large scale application. The classical combination dextran-polyethylene glycol gave promising results; a partition coefficient of about 0.02 was obtained for the distribution of the gp51 between the top and combined inter- and bottom phases. In a single extraction step it was possible to obtain 45% of the glycoprotein in a small volume bottom phase and at the same time about 15-fold purified. That should be compared with a recovery of less than 20% with the conventional centrifugation procedures. It is concluded that extraction in phase systems based on water soluble polymers is a methodology well suited for the concentration and purification of BLV-gp51.
Animals↗
[Omeprazole (20 mg daily) compared to ranitidine (150 mg twice daily) in the treatment of esophagitis caused by reflux. Results of a double-blind randomized multicenter trial in France and Belgium].
We report the results of a trial of omeprazole 20 mg daily versus ranitidine 150 mg b.i.d. in the short-term management of erosive or ulcerative esophagitis. The principal aim of the trial was to assess the healing rates of the esophageal lesions. The trial was conducted in 19 centers (16 in France and 3 in Belgium). The lesions of the esophageal mucosa were defined as follows: grade 2 (n = 112), round or linear erosions; grade 3 (n = 33), confluent erosions affecting the total esophageal circumference; or grade 4 (n = 11), erosions as described above plus deep ulcerations or peptic stenosis which did not need endoscopic dilatation. The main criterion was the complete healing of esophageal lesions after 4 weeks of treatment. Patients were randomly allocated to double-blind treatment with omeprazole or ranitidine. Clinical and endoscopic examinations were done on inclusion in the trial and at day 29 +/- 6, and again at day 57 +/- 6 if esophagitis was unhealed. No patient was excluded from the analysis on an "intention-to-treat" basis, and 25 patients were excluded from the "per protocol" analysis, mainly because of poor compliance with the trial protocol. The healing rate at weak 4 was 50 of 62 patients (81 p. 100) treated with omeprazole and 31 of 69 patients (45 p. 100) with ranitidine (p less than 0.001). The corresponding figures at week 8 were 58 of 61 (95 p. 100) and 40 of 61 (65 p. 100) (p less than 0.001).
Belgium↗
Laboratory tests in patients with suspected acute appendicitis.
The clinical usefulness of preoperative determination of total and differential white blood cell count and C-reactive protein was studied in 113 patients undergoing emergency appendectomy for suspected acute appendicitis. The diagnosis was confirmed in 86 (76%) of the patients. In all 86 cases at least one of the three laboratory tests gave an abnormal result. The highest incidence of abnormal results was found in the most advanced stages of inflammatory reaction in the appendix. In nine of the 27 patients with histologically normal appendix all three laboratory parameters were normal. The "negative appendectomy rate" would have fallen from 24% to 16% in this study if the patients with negative results in all three tests had not been operated on.
Acute Disease↗
Eating problems and nutritional status during hospital stay of patients with severe stroke.
Eating problems and nutritional status were studied in a consecutive series of patients who had had strokes. From this cohort, 32 subjects (mean age 73 years) with a hospital stay of 21 days or more are described. Eating problems were identified by direct participant observations of the patients' eating behavior, interviews on admission, inspections of the mouth, and discussions with the patients. Nutritional status was assessed by weight, triceps skinfold thickness (TSF), arm muscular circumference (AMC), plasma albumin, serum transferrin, and plasma prealbumin on admission and then weekly. Eating problems were identified in 27 patients. In a general linear hypothesis program, poor nutritional status 3 weeks after admission was found to be associated with (in decreasing order) low self-care performance, poor nutritional status on admission, male sex, intravenous energy-containing fluids, advanced age, paresis of the right arm, and eating problems. Factors other than eating problems seem to be important for undernutrition in patients with strokes during hospital stay.
Cerebrovascular Disorders↗
Prevalence of hemochromatosis.
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Hemochromatosis↗
[Assessment in practice--one must dare to make one's own decisions. Interview by Britta Nilsson].
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Adolescent↗
Anthracycline-DNA interactions studied with linear dichroism and fluorescence spectroscopy.
DNA-binding geometry and dynamics of a number of anthracyclines, including adriamycin and 4-demethoxydaunorubicin, interacting with DNA have been studied by means of linear dichroism and fluorescence techniques. The anthracycline chromophore is found to be approximately parallel to the plane of the DNA bases and to have a restricted mobility, as would be expected for an intercalative binding mode, but there are variations between different directions in the chromophore as well as between the drugs. From dichroic spectra of adriamycin in an anisotropic host of poly(vinyl alcohol), absorption components corresponding to transitions with mutually orthogonal polarizations have been resolved. These can be exploited to determine the orientations of the two chromophore axes in the DNA complex relative to the DNA helix axis. In a certain binding regime the long axis of the bound anthracycline chromophores (with the exception of 4-demethoxydaunorubicin) is found to be approximately 10 degrees closer to perpendicular to the helix axis than are the DNA bases. This demonstrates that the average base tilt is at least 10 degrees. By contrast, the short axis of the aglycon moiety is found to be tilted some 20-30 degrees from perpendicular. This may be because it is probing a base direction with a more pronounced, static or dynamic, inclination than the average in DNA. The drug orientation and the DNA orientation (reflecting flexibility) are observed to vary differently and nonmonotonically with binding ratio, suggesting specific binding and varying site geometries.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibiotics, Antineoplastic↗
Direct photoaffinity labeling of ribonucleotide reductase from Escherichia coli using dTTP: characterization of the photoproducts.
Subunit B1 of Escherichia coli ribonucleotide reductase contains one type of allosteric binding site that controls the substrate specificity of the enzyme. This site binds the allosteric effector dTTP as well as other nucleoside triphosphates. Cross-linking of dTTP to protein B1 by direct photoaffinity labeling, as well as the isolation and sequence determination of the labeled tryptic peptide, has recently been reported [Eriksson, S., Sjöberg, B.-M., Jörnwall, H., & Carlquist, M. (1986) J. Biol. Chem. 261, 1878-1882]. In this study, we have further purified the dTTP-labeled peptide and characterized it using UV spectroscopy. Two types of dTTP-cross-linked peptide were found: one having an absorbance maximum at 261 nm typical for a dTTP spectrum, i.e., containing an intact 5,6 double bond, and one minor form with low absorbance at 261 nm. In both cases, the same amino acid composition was found, corresponding to the peptide Ser291-X-Ser-Gln-Gly-Gly-Val-Arg299 in the B1 sequence with X being Cys-292 cross-linked to dTTP. Isotope labeling experiments revealed that one proton in the 5-methyl group of thymine was lost during photoincorporation. Therefore, the cross-linking occurs via the 5-methyl group to Cys-292 in a majority of incorporated dTTPs, but a second, possibly 5,6-saturated form of incorporated nucleotide was also detected. The reasons for the high stereospecificity of the reaction and the possible structure of the allosteric site of protein B1 are discussed.
Affinity Labels↗
Deoxycytidine kinase from human leukemic spleen: preparation and characteristics of homogeneous enzyme.
Deoxycytidine kinase from human leukemic spleen has been purified 6000-fold to apparent homogeneity with an overall yield of 10%. The purification was achieved by using DEAE chromatography, hydroxylapatite chromatography, and affinity chromatography on dTTP-Sepharose. Only one form of deoxycytidine kinase activity was found during all the chromatographic procedures. The subunit molecular mass, as judged by sodium dodecyl sulfate--polyacrylamide gel electrophoresis, was 30 kilodaltons. The pure enzyme phosphorylates deoxycytidine, deoxyadenosine, and deoxyguanosine, demonstrating for the first time that the same enzyme molecule has the capacity to use these three nucleosides as substrates. The apparent molecular weight of the active enzyme, determined by gel filtration and glycerol gradient centrifugation, was 60,000. Thus, the active form of human deoxycytidine kinase is a dimer. The kinetic behavior of pure human deoxycytidine kinase was studied in detail with regard to four different phosphate acceptors and two different phosphate donors. The apparent Km values were 1, 20, 150, and 120 microM for deoxycytidine, arabinosylcytosine, deoxyguanosine, and deoxyadenosine, respectively. The Vmax values were 5-fold higher for the purine nucleosides as compared to the pyrimidine substrates. We observe competitive inhibition of the phosphorylation of one substrate by the presence of either of the three other substrates, but the apparent Ki values differed greatly from the corresponding Km values, suggesting the existence of allosteric effects. The double-reciprocal plots for ATP-MgCl2 as phosphate donor were convex, indicating negative cooperative effects. In contrast, plots with varying dTTP-MgCl2 concentration as phosphate donor were linear with an apparent Km of 2 microM. The enzyme activity was strongly inhibited by dCTP, in a noncompetitive way with deoxycytidine and in a competitive way with ATP-MgCl2.
Binding, Competitive↗
Occlusion of rostroventral 3rd ventricle abolishes drinking but not AVP release in response to central osmotic stimulation.
Dogs were implanted with a device for chronic cannulation of the anterior part of the 3rd ventricle (A3V). Intracerebroventricular (i.c.v.) infusion of artificial cerebrospinal fluid (CSF) containing 0.35 M NaCl into the A3V of 7 normally hydrated dogs induced thirst (average water intake 11.8 +/- 2.0 ml.kg-1 b. wt.) and significantly increased arginine-vasopressin (AVP) concentration in the blood plasma from 3.4 +/- 0.3 to 8.2 +/- 1.2 pg.ml-1. When repeating the i.c.v. hypertonic infusion at intervals of one week or more in two dogs, its dipsogenic effect vanished within 3-5 months. X-ray analysis revealed an occlusion of the rostroventral part of the A3V. Subsequent controls on 3 other dogs confirmed that the dipsogenic response to i.c.v. osmotic stimulation was abolished in association with similar partial occlusions of the A3V. However, this stimulus still produced a significant increase of plasma AVP from 3.7 +/- 0.5 to 5.7 +/- 0.7 pg.ml-1 in the 5 dogs. Control of drinking in these dogs was otherwise unimpaired as indicated by their normal plasma osmolalities. Histological examination revealed that the loss of the dipsogenic response to i.c.v. infusion of 0.35 M NaCl was in each case associated with fibrinous occlusion of the A3V between its rostral wall and the mass intermedia, preventing the passage of the infusate to the supraoptic and infundibular recesses.
Animals↗
Gallium-67 scintigraphy in acute pancreatitis.
Acute pancreatitis is a serious surgical problem with a high incidence of mortality. Both ultrasound and X-ray CT have problems in identifying the extent and severity of the disease and the response to therapy. 67Ga-citrate has been used in 21 patients with clinically diagnosed acute pancreatitis: 9 patients had X-ray CT and 15 had US examination. Gallium scans were more sensitive than X-ray CT and US in detecting the extent and severity of acute pancreatitis. In addition, gallium was helpful to monitor the response to therapy when the scan was repeated at various intervals in three patients. A subtraction technique using 99mTc-tin colloid and 67Ga-citrate was helpful to mask the liver uptake of gallium and clearly identify the extent of acute pancreatitis.
Acute Disease↗
Deoxycytidine kinase is constitutively expressed in human lymphocytes: consequences for compartmentation effects, unscheduled DNA synthesis, and viral replication in resting cells.
Deoxycytidine kinase specific activity was high in human peripheral lymphocytes and increased less than 2-fold when the lymphocytes were stimulated by phytohemagglutinin A. Ion-exchange chromatography showed the same profile of deoxycytidine kinase activity in resting and proliferating cells. This enzyme could also efficiently phosphorylate deoxyadenosine and deoxyguanosine. In contrast, the thymidine kinase activity was very low in resting peripheral lymphocytes and increased more than 40-fold upon stimulation. Similar relative changes in the activities of the two enzymes were observed in human T-lymphoblast cells (CCRF-CEM) separated by centrifugal elutriation into cells of different cell cycle phases. The ratio of deoxycytidine to thymidine kinase activities is 20:1 in extracts from resting human lymphocytes and 1:2 in PHA-stimulated cells. This drastic change in deoxyribonucleoside phosphorylating activities during the cell cycle in human lymphocytes is of importance for studies on unscheduled DNA synthesis, for the design of therapies to interfere with viral DNA metabolism, and for a correct interpretation of the compartmentation effects observed in DNA precursor metabolism.
Cell Compartmentation↗
Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ.
Lung function, smoking, age and mortality data in 158 adult severe alpha 1-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV1 value was significantly associated with increased mortality (p less than 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV1 values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV1 values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV1 levels (p = 0.008) and higher mortality (p less than 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV1 level were not statistically significant (p = 0.9 and p greater than 0.25, respectively). Cross-sectional analysis of the initial FEV1 values indicated a significant decline (p less than 0.005) of FEV1 with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV1 rates of decline in 80 cases with follow-up FEV1 measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.
Adolescent↗
Pulmonary-artery cineangiocardiography and echocardiography for detection of cardiac sources of cerebral embolism.
Sixty-two patients with ischemic stroke possibly due to embolism of cardiac origin were investigated by pulmonary artery-cineangiography (PACAC) and echocardiography (UCG) to detect intracardiac thrombi. The proportion of intracardiac thrombi found by PACAC was 31% and by UCG 15%. The presence or absence of atrial fibrillation correlated well with PACAC findings of an intraventricular clot but poorly with UCG. Similarly, there was a significant association between ischemic heart disease and intraventricular thrombi detected by PACAC investigations but not with the results obtained by UCG. PACAC seems superior to UCG in the detection of intracardiac thrombi after possible embolic stroke.
Adult↗
Clinical and immunological features of Sjögren's syndrome in patients with primary biliary cirrhosis with emphasis on focal sialadenitis.
Serological and pathological findings in 21 patients with primary Sjögren's syndrome (primary SS) were compared with those in 32 patients with primary biliary cirrhosis (PBC). In ELISA, anti-SS-B/La antibodies were detected in sera from 14 (67%) of the patients with primary SS, but only from 12 (38%) of those with PBC. With the Ouchterlony test, anti-SS-A/Ro antibodies were found in sera from 15 (71%) of the primary SS patients, but in no PBC patient. Of those PBC patients investigated prospectively with objective tests, four of 11 (36%) had keratoconjunctivitis sicca, and five of 15 (33%) had pathological sialometry results. In contrast, all PBC patients but one (i.e., 14 of 15 or 93%) showed evidence of focal sialadenitis. In immunochemical study of PBC patients, IgM immunoreactivity was found in the stroma, particularly adjacent to excretory ducts and acini in salivary glands (5 of 5), whereas no such IgM deposits were observed in patients with primary SS (3 of 3), nor in healthy controls (n = 20). We conclude that the frequency of anti-SS-A/Ro and anti-SS-B/La antibodies in serum is lower in PBC patients than in patients with primary SS. The incidence of focal sialadenitis is high in PBC, though only one third of the PBC patients studied here showed clinical evidence of glandular dysfunction. With immunochemical techniques, sialadenitis associated with PBC is distinguishable by its significant IgM reaction from sialadenitis in primary SS.
Aged↗
Monoamine metabolite concentrations and cholinesterase activities in cerebrospinal fluid of progressive dementia patients: relation to clinical parameters.
Forty-five well clinically characterized patients with progressive dementia were investigated for lumbar cerebrospinal fluid (CSF) monoamine metabolites and cholinesterase activities. Monoamine concentrations were determined by reverse phase liquid chromatography with electrochemical detection and the cholinergic enzymes were measured photometrically. Firstly, all clinical and CSF parameters were studied in statistical cluster analyses to detect groups of variables which demonstrated a high correlation with respect to each other. The CSF transmitter markers were then used in multiple regression models to explain the variance of clinical variables as chosen from the cluster analyses. The degree of dementia, as assessed by global deterioration score (GDS) and activity in daily life (ADL) status, as well as the Alzheimer-related symptoms dyspraxia and dysphasia, were associated with low AChE activities in CSF. A presumed subgroup of dementia patients clinically characterized by asymmetry of neurological signs, increased unilateral tonus, stepwise progression, and high Hachinski score, showed low HVA concentrations in CSF. These data suggest a coupling of clinical/neurological parameters to different CSF transmitter profils and, thus, that CSF biochemical parameters are of use as antemortem markers in dementia conditions.
Acetylcholinesterase↗