PubMed Health⌕ Search

Biomedical subjects

E Johnsson

Publications and source records attributed to E Johnsson.

At least 19 recordsLinked to original sources
PubMed2001

IgM and stromal cell-associated heparan sulfate/heparin as complement-independent ligands for CD19.

The more severe phenotype of mice lacking CD19 as compared to CD21 suggests that a complement-independent ligand for the CD19/CD21 complex exists. We sought ligands for CD19 by examining binding reactions with fusion proteins comprised of the extracellular region of CD19 and the Fc region of IgG1. A fusion protein containing the third extracellular domain (D3-Fc) bound to WEHI-231 cells, and this was competed by soluble IgM. This function of IgM was confirmed by the binding of D3-Fc to beads coated with IgM. A second ligand for D3-Fc was found on stromal cells, and was shown to be heparin/heparan sulfate. These two ligands would be considered to reside on follicular dendritic cells, and may account for the observed ability of D3-Fc to bind to sites in germinal centers containing these cells.

Animals↗
PubMed2001

Preoperative adjuvant radiochemotherapy may increase the risk in patients undergoing thoracoabdominal esophageal resections.

BACKGROUND/AIM: Fatigue and malaise are common symptoms after radiochemotherapy which could affect patients' working capacity and add to the subsequent postoperative risk. The aim of the study was to investigate whether neoadjuvant radiochemotherapy in patients scheduled for a thoracoabdominal resection impairs their working capacity and adds to the postoperative risk. PATIENTS AND METHODS: 29 patients with resectable tumors (T(3) or N(1)) and a working capacity of > or =80 W on a bicycle test were included into the study. The tumor stage was determined by endoscopic ultrasound and computed tomography scan. The patients were given neoadjuvant radiochemotherapy during 38 days, consisting of two cycles of 5-fluorouracil (1,000 mg/m(2)) daily during 5 days and cisplatinum (100 mg/m(2)) on two occasions. Accelerated radiochemotherapy to a total dose of 40.8 Gy was given. Surgery was planned 4-6 weeks after completion of therapy. The patients had a bicycle test before induction of neoadjuvant treatment and 2-5 days prior to the operation. RESULTS: Three patients died already during the course of neoadjuvant treatment. The 26 remaining patients who had a bicycle test decreased their working capacity by a mean of 30 W (p < 0.0001). Ten patients had a decrease of their working capacity to < or = 90 W, of whom 6 died within 3 months postoperatively, and of the patients who had the working capacity decreased to < or = 80 W, 4 out of 5 died during the corresponding postoperative period. None of the patients, who performed >100 W at the second preoperative bicycle test died. CONCLUSIONS: Preoperative adjuvant radiochemotherapy, according to the present schedule, clearly exerts a detrimental effect on the patients' working capacity. A physical performance, at the time of the operation, < or = 80-90 W strongly predicts the subsequent postoperative risk. Similar adjuvant therapies may, therefore, in fact be harmful to some patients scheduled for a thoracoabdominal resection.

Adenocarcinoma↗
PubMed2000

Human complement regulators: a major target for pathogenic microorganisms.

The C3 convertases of the human complement system are controlled by fluid-phase and membrane proteins in the RCA (regulators of complement activation) family. Accumulated data show that many pathogenic microorganisms interact with these complement regulators. Recent advances in this field include determination of the crystal structure of the binding domains in the measles virus receptor CD46 and identification of a CD46 transgenic mouse line that is sensitive to measles virus. Moreover, recent findings support the hypothesis that pathogenic bacteria binding fluid-phase RCA proteins exploit these proteins to escape complement attack. These studies provide novel insight into the interplay between pathogens and the innate immune system and may have implications for the plans to use animals expressing an RCA protein for xenotransplantation.

Antigens, CD↗
PubMed2000

Unrestricted pore area (A0/Deltax) is a better indicator of peritoneal membrane function than PET.

BACKGROUND: How to measure the peritoneal exchange in uremic patients treated with peritoneal dialysis (PD) is still a matter of controversy. Most clinics use the peritoneal equilibration test (PET), but from a theoretical point of view, it would be more appropriate to determine the "area" parameter, A0/Deltax. The latter reflects the total unrestricted pore area per centimeter diffusion distance and can be obtained by three-pore analysis using, for example, the PD capacity test (PDC). To evaluate the different estimates of peritoneal function, PET data and the A0/Deltax parameters were compared with the independently determined uptake of a small diffusible tracer, iohexol (molecular weight of 821 D), from the abdominal cavity to blood. METHODS: Fourteen patients on routine PD underwent determinations of PET and A0/Deltax using PDC. Within a month, the two-hour uptake of iohexol (6 mg/mL) was also determined from the plasma iohexol concentration following abdominal filling. RESULTS: A strong correlation was found between the rate of iohexol plasma concentration increase (k30-120) and A0/Deltax (A0/Deltax = 76,300. k30-120 - 1.56; r2 = 0.799; N = 14) for the 2 L dwell, while the PET data were far less related to iohexol uptake (D/DPurea, r2 = 0.409; D/Pcreatinine, r2 = 0.436; and D/D0glucose, r2 = 0.015, respectively). CONCLUSION: The "area" parameter, A0/Deltax, is superior to the more widely used routine PET as an indicator of peritoneal membrane function. In addition, the concept of A0/Deltax has the virtue of supplying quantitative information about the peritoneal pathophysiology and physiology.

Adult↗
PubMed1999

An IgA-binding peptide derived from a streptococcal surface protein.

Surface proteins that bind to the Fc part of human IgA are expressed by many strains of Streptococcus pyogenes, a major human pathogen. Studies of these proteins have been complicated by their size and by their ability to bind human plasma proteins other than IgA. Here, we describe a synthetic 50-residue peptide, derived from streptococcal protein Sir22, that binds human IgA but not any of the other plasma proteins known to bind to Sir22. The peptide binds serum IgA and secretory IgA and binds IgA of both subclasses. Evidence is presented that the peptide folds correctly both in solution and when it is immobilized and that it readily renatures after denaturation. Together, these data indicate that the peptide corresponds to a protein domain that binds IgA with high specificity. This is the first report of an IgA-binding domain that retains its properties in isolated form.

Bacterial Outer Membrane Proteins↗
PubMed1999

Improved clearance of iohexol with longer haemodialysis despite similar Kt/V for urea.

BACKGROUND: The efforts to improve the quality of haemodialysis (HD) has renewed the interest in the consequences of blood-flow distribution for removal of solutes. METHODS: To test the effects of HD time per se, 10 patients were studied in a cross-over fashion with HD for 3 h and 1 week later for 6 h, with similar blood urea Kt/Vs, achieved by adjusting the blood flow rate to 290 and 120 ml/min respectively. Injections of iohexol (MW 821 Dalton) were given 2 days prior to the dialysis sessions. Blood samples were taken before, during (6/HD), 1 and 24 h after the HD and analysed for concentrations of urea and iohexol. A urea on-line monitor (Gambro) was used for continuous recordings and sampling of dialysate. RESULTS: According to the study design the blood Kt/V for urea (Daugirdas II) was similar for 3 and 6 h HD, close to 1.0 (n.s), while the removed mass of urea showed that Kt/V was slightly and significantly higher for the 6 h HD. The 'apparent' mass of iohexol, defined as plasma concentration times estimated distribution volume, fell to 29% and 21% of pre-dialysis levels after 3 h and 6 h HD, respectively (P<0.01), but increased after HD, and more so after the short dialysis, reaching 46% of the predialysis mass 24 h after 3 h HD vs. 36% after 6 h HD (P<0.05). The removed mass of iohexol was 920+/-110 mg with 6h HD and 700+/-81 mg with 3h HD, (P<0.01). Thus, the longer dialysis removed 32% more iohexol despite similar blood Kt/V for urea. CONCLUSION: The treatment time per se affects solute removal despite similar blood Kt/V for urea. This is particularly true for an intermediate-size molecule like iohexol.

Aged↗
PubMed1998

Role of the hypervariable region in streptococcal M proteins: binding of a human complement inhibitor.

Antigenic variation allows pathogenic microorganisms to evade the immune system of the infected host. The variable structure must play an important role in pathogenesis, but its function is in most cases unknown. Here, we identify a function for the surface-exposed hypervariable region of streptococcal M5 protein, a virulence factor that inhibits phagocytosis. The hypervariable region of M5 was found to bind the human complement inhibitor FHL-1 (factor H-like protein 1), a 42-kDa plasma protein. Plasma absorption experiments with M5-expressing bacteria showed that the interaction with FHL-1 occurs also under physiologic conditions. Studies of another extensively characterized M protein, M6, indicated that this protein also has a binding site for FHL-1 in the hypervariable region. The complement-inhibitory function of FHL-1 was retained after binding to streptococci, suggesting that bound FHL-1 protects bacteria against complement attack. All available data now indicate that FHL-1, or another human complement inhibitor, binds to the hypervariable region of M proteins. These findings provide insights into the forces that drive antigenic variation and may explain why the hypervariable region of M protein is essential for phagocytosis resistance. Moreover, these data add to a growing body of evidence that human complement inhibitors are major targets for pathogenic microorganisms.

Antigenic Variation↗
PubMed1998

Identification of a domain in human factor H and factor H-like protein-1 required for the interaction with streptococcal M proteins.

The plasma protein factor H (FH) inhibits the alternative pathway of complement activation. Previous work has shown that FH binds to group A streptococci and that the interaction does not interfere with the complement-inhibitory capacity of FH. In this work, we report a molecular analysis of this interaction. In absorption experiments with human plasma, M protein-expressing group A streptococci bound both FH and FH-like protein-1 (FHL-1), an active 42-kDa splice product of the FH-gene transcript comprising the first 7 of its 20 short consensus repeat (SCR) domains. rFHL-1 also bound to M protein-expressing streptococci, but rFH fragments containing SCR 1-5 or SCR 1-6 did not. rFHL-1 bound to purified M5 protein with an affinity that was higher than the value calculated for the interaction between FH and M5 protein. The binding of radiolabeled rFHL-1 to immobilized M5 was blocked completely by unlabeled rFHL-1, but was inhibited only partially by SCR 1-6, emphasizing the importance of SCR 7 for the interaction. In experiments with the FH-related proteins FHR-3 and FHR-4, only the former bound to M protein-expressing streptococci, again pointing to an involvement of SCR 7, since FHR-3, but not FHR-4, contains a domain that is similar to SCR 7. Finally, the interaction between rFHL-1 and purified M5 protein was inhibited by heparin, which binds FH via SCR 7. Together, these data indicate that the interaction between streptococcal M proteins and FH or FHL-1 requires SCR 7.

Absorption↗
PubMed1998

Glomerular charge selectivity for proteins larger than serum albumin as revealed by lactate dehydrogenase isoforms.

It is well known that macromolecules like albumin are markedly restricted in their passage across the glomerular capillary wall. However, the relative importance of solute size, charge and shape is currently debated since much of the previous work is based on dextran in neutral or charge-modified forms. These polymers have certain drawbacks that make them less suitable for analysis of capillary permeability and the notion of a glomerular charge barrier has therefore been questioned. Moreover, macromolecules larger than albumin (mol. wt. 69,000) have been suggested to pass through nonselective 'shunt' pathways. In order to study glomerular permeability, isolated rat kidneys were perfused with albumin solutions containing trace amounts of two differently radiolabelled isoenzymes of lactate dehydrogenase (LDH) at low temperature to inhibit tubular function. The isoenzymes have similar size (mol. wt. 140,000) and shape but differ in charge, one carrying a negative net surface charge (LDH1, -19) and the other being slightly cationic (LDH5, +2). The urine and perfusate samples were subjected to high pressure liquid chromatography (HPLC) gel-filtration to allow for measurements of intact LDH. The fractional clearance was 0.11% +/- 0.04% for the anionic LDH1 and 0.56% +/- 0.07% for LDH5, whereas that for albumin was 0.21% +/- 0.03% at a glomerular filtration rate of 0.11 +/- 0.01 mL min-1 g-1 kidney wet weight. The results were analysed using a homogenously charged membrane model and are compatible with a charge density of 35 mEq L-1, with 95% confidence interval of 26-41 mEq L-1. These findings suggest a significant glomerular charge selectivity for proteins substantially larger than albumin. The charge density is, however, far less than estimated from dextran studies.

Albumins↗
PubMed1998

p53-dependent and -independent differentiation of leukemic U-937 cells: relationship to cell cycle control.

Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used for mediating G1 arrest. The differentiation response to transfected p53 with or without INF-gamma was inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine) in a dose-dependent manner. In contrast, the differentiation response of p53-negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated differentiation could be achieved in cells arrested in G1 by concomitant incubation with cAMP-inducing agents, indicating that differentiation can occur in the absence of proliferation. In conclusion, the results of this study indicate that p53-dependent and -independent differentiation can occur independently of cell cycle regulation.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Altered expression of the retinoblastoma tumor-suppressor gene in leukemic cell lines inhibits induction of differentiation but not G1-accumulation.

The retinoblastoma tumor-suppressor gene, RB, has been implicated in tumor suppression, in regulation of the cell cycle, and in mediating cell differentiation. RB is necessary for hematopoiesis in mice, and aberrant RB-expression is associated with the progress and prognosis of leukemia. We have used antisense oligonucleotides, established clones stably expressing an antisense RB construct, and also established clones over expressing the retinoblastoma protein (pRb) to study the role of RB expression in monocytic differentiation induced by all-trans retinoic acid (ATRA) or 1-alpha-25-dihyroxycholecalciferol (Vit D3) in the monoblastic cell line U-937 and erythroid differentiation induced by transforming growth factor beta1 (TGFbeta1) and hemin in the erythroleukemic cell line K562. A reduction in pRb production in antisense RB-transfected U-937 clones was shown. Antisense oligonucleotides as well as expression of the antisense RB construct suppressed differentiation responses to ATRA or Vit D3, as judged by the capability to reduce nitro blue tetrazolium, by the appearance of monocyte-related cell surface antigens and by morphologic criteria. K562 cells showed decreased differentiation response to TGFbeta1, but not to hemin, when incubated with antisense oligonucleotides. U-937 antisense RB-transfected cells were also suppressed in their ability to upregulate levels of hypophosphorylated pRb when induced to differentiate. Although U-937 cells incubated with antisense oligonucleotides and clones expressing the antisense RB construct were hampered in their ability to differentiate on incubation with ATRA or Vit D3, the induced G0/G1-accumulation was similar to differentiating control cells treated with ATRA or Vit D3. Intriguingly, U-937 clones overexpressing RB were also inhibited in their differentiation response to ATRA or Vit D3 but not inhibited in their ability to respond with G0/G1 accumulation when induced with these substances. The results indicate that pRb plays a role in induced differentiation of U-937 cells as well as K562 cells involving mechanisms that, at least partially, are distinct from those inducing G1 accumulation.

Animals↗
PubMed1997

High glomerular permeability of bikunin despite similarity in charge and hydrodynamic size to serum albumin.

Bikunin is a chondroitin-sulphate containing serum protein with a Stokes-Einstein radius and a negative net charge close to those of serum albumin. The plasma half life of bikunin is about 10 minutes, and approximately half of its clearance occurs in the kidneys. The quantitative role of glomerular filtration in the renal clearance of this protein has not been determined. To assess the glomerular permeability of bikunin we used isolated rat kidneys that were perfused with an albumin solution. The metabolic activities of the tubuli were inhibited by low temperature (8 degrees C). The clearances of radiolabeled bikunin and albumin were repeatedly determined under identical conditions. The fractional clearance of bikunin was found to be 80 times higher than that of albumin: 15% +/- 1% versus 0.18% +/- 0.02%. This value for bikunin can fully account for its renal clearance in vivo. It has previously been shown that uncharged flexible solutes, such as dextrans, have higher renal clearances than globular molecules with similar radii. The high glomerular permeability of bikunin is therefore probably due to its elongated and flexible configuration. Moreover, the observed clearance value of the anionic molecule bikunin is close to that of a neutral flexible dextran of similar size, indicating that the charge of bikunin is of little importance for its glomerular permeability.

Animals↗
PubMed1997

Suicide attempts in a cohort of drug abusers: a 5-year follow-up study.

A group of 125 drug abusers admitted consecutively for detoxification and short-term rehabilitation were followed up 5 years after discharge. They were asked about possible suicide attempts in a semi-structured face-to-face interview. Nearly half of the group (45%) reported having attempted suicide at some point in their life. The most common reasons given were the loss of a person whom they loved, and feelings of loneliness. Only three respondents reported using their drug of choice in the attempt(s). The suicide attempters were more often found to have been in child psychiatric treatment earlier, and to have experienced loss of significant others in childhood, than those who did not report attempting suicide. At follow-up the suicide attempters indicated that they experienced more depressive moods and more severe psychological problems than those who had never made a suicide attempt. The importance of assessing the risk of suicide attempts among drug addicts in order to be able to take measures to prevent future suicidal behaviour is emphasized.

Adult↗
PubMed1997

Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin.

C4BP (C4b-binding protein) is a high-molecular-weight plasma protein that inhibits the classical pathway of complement activation. Recent experiments have demonstrated that C4BP binds to many strains of the gram-positive bacterium Streptococcus pyogenes, a major respiratory tract pathogen. Binding to S. pyogenes was shown to be due to members of the M protein family, a group of surface proteins important for virulence. Here we report that human C4BP also binds to all clinical isolates of the gram-negative bacterium Bordetella pertussis, the etiologic agent of whooping cough. In addition, binding of C4BP was demonstrated for other Bordetella species that can cause disease in humans. Characterization of different B. pertussis mutants showed that the binding of C4BP is strongly dependent on the expression of the cell surface protein filamentous hemagglutinin, a well-known virulence factor. Inhibition experiments suggested that B. pertussis and S. pyogenes bind to the same region in C4BP. The finding that B. pertussis and S. pyogenes both have the ability to bind human C4BP suggests that these two unrelated respiratory tract pathogens may use a common mechanism during the establishment of an infection.

Adhesins, Bacterial↗
PubMed1997

The tumor suppressor gene p53 can mediate transforming growth [corrected] factor beta1-induced differentiation of leukemic cells independently of activation of the retinoblastoma protein.

Although the involvement of the tumor suppressor gene p53 in normal hematopoiesis is uncertain, it can give rise to differentiation signals in leukemic cells. It is not clear, however, whether differentiation merely is a consequence of the ability of p53 to arrest cell proliferation or whether hitherto unknown molecular mechanisms are responsible for the p53-mediated differentiation. To further explore the role of p53 in leukemic cell differentiation, we investigated whether transforming growth factor beta1 (TGF-beta1), a cytokine involved in cell cycle control at several levels, can cooperate with wild-type p53 to induce differentiation of monoblastic U-937 and erythroleukemic K562 cells. Indeed, wild-type p53-expressing cells were found to be more sensitive to TGF-beta1-induced differentiation than control cells, lending support to the idea that p53 is of importance for differentiation induction of leukemic cells. In addition, it is shown that TGF-beta1 can suppress p53-mediated cell death, thus reinforcing the differentiation response. The cyclin-dependent kinase inhibitor p21 and the retinoblastoma protein (pRb) are downstream effectors of p53-mediated growth arrest. Therefore, the roles for these molecules in p53-mediated differentiation were examined. The p53-dependent signals of differentiation were associated with induction of p21 in both cell lines investigated. However, activation of pRb by induced hypophosphorylation and concomitant decreased growth rate on p53-mediated differentiation was observed only in U-937 cells expressing an inducible, temperature-sensitive form of p53 but not in K562 cells constitutively expressing p53. Thus, our data suggest a role for p53 in the regulation of differentiation in leukemic cells that can be independent of its ability to activate pRb and arrest cell proliferation.

Apoptosis↗