| 1. |
- Bućin, Dragan, et al.
(författare)
-
Desensitization and Heart Transplantation of a Patient With High Levels of Donor-Reactive Anti-Human Leukocyte Antigen Antibodies.
- 2010
-
Ingår i: Transplantation. - 1534-6080. ; 90, s. 1220-1225
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND.: To prepare a highly immunized recipient for heart transplantation, reduction of high levels of cytotoxic antibodies against human leukocyte antigen (HLA) was deemed essential to prevent antibody-mediated graft failure. METHODS.: Antibodies were analyzed by lymphocytotoxic and solid-phase assays. The pretransplant desensitization treatment protocol included daily tacrolimus and mycophenolate mofetil, weekly protein-A immunoadsorption (IA), intravenous immunoglobulin, and daclizumab. Posttransplant treatment consisted of tacrolimus, mycophenolate mofetil, prednisolone, IA, and daclizumab. RESULTS.: During pretransplant desensitization, each of the weekly immunoadsorption treatments reduced anti-HLA antibody levels by 50% to 70%, but they returned to the pretreatment level within 1 week as measured by flow cytometry. Cytotoxic antibodies remained reduced. After perioperative immunoadsorption, the donor-reactive antibodies (DRAs) were reduced to low levels. The patient underwent successful heart transplantation after 6 weeks on a waiting list. During the first week posttransplant, DRAs remained low. However, after the first week, anti-HLA DRAs reappeared and increased slightly over a 3-week period and then decreased slowly. Cytotoxic crossmatches were negative before and 3 week after transplantation. No clinical rejection was encountered. The patient was doing well 3 years after transplantation, and yearly clinical cardiac investigations were all normal. Three hyperimmunized patients have now undergone successful heart transplantation at our center using this desensitization protocol. CONCLUSIONS.: IA in combination with pretransplant immunosuppressive drug treatment temporarily reduces antibody levels. The therapeutic levels of drug treatment at the time of transplantation may be of crucial importance. The treatment protocol resulted in freedom from rejection and other clinical adverse events.
|
|
| 2. |
- Bucin, Dragan, et al.
(författare)
-
Heart transplantation across the antibodies against HLA and ABO
- 2006
-
Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 19:3, s. 239-244
-
Tidskriftsartikel (refereegranskat)abstract
- We have intentionally performed heart transplantation in a 5-year-old child, despite the most unfavourable risk factors for patient survival; the presence of high level of antibodies against donor's human leucocyte antigen (HLA) class I/II and blood group antigens. Pretransplant treatment by mycophenolate mofetil, prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A immunoadsorption (IA) and plasma exchange reduced antibody titres against the donor's lymphocytes from 128 to 16 and against the donor's blood group antigen from 256 to 0. The patient was urgently transplanted with a heart from an ABO incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol was used. No hyperacute rejection was seen. Antibodies against the donor's HLA antigens remained at a low level despite three acute rejections. Rising anti-A(1) blood group antibodies preceded the second rejection and were reduced by two blood group-specific IAs and remained at a low level. The patient is doing well despite the persistence of donor-reactive antibodies.
|
|
| 3. |
- Godaly, Gabriela, et al.
(författare)
-
Fimbrial lectins influence the chemokine repertoire in the urinary tract mucosa.
- 2007
-
Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 71:8, s. 778-786
-
Tidskriftsartikel (refereegranskat)abstract
- The defense against mucosal infections relies on chemokines that recruit inflammatory cells to the mucosa. This study examined if the chemokine response to uro-pathogenic Escherichia coli is influenced by fimbrial expression. The CXC (CXCL1, CXCL5, CXCL8, CXCL9, CXCL10) and CC chemokines (CCL2, CCL3, CCL5) were quantified after in vitro infection of uro-epithelial cells with a fimbriated E. coli pyelonephritis isolate, or with P or type 1 fimbriated transformants of an avirulent E. coli K-12 strain. The response profile was shown to vary with the fimbrial type. Type 1 fimbriated E. coli elicited mainly CXCL1 and CXCL8, whereas P fimbriated E. coli stimulated CCL2 and CCL5 and class II were more potent chemokine inducers than class III P fimbriae. Chemokines were also quantified in urine samples from 73 patients with febrile urinary tract infection, and analyzed as a function of disease severity and fimbrial expression by the strain infecting each patient. A complex CXC and CC chemokine response was detected in patient urine, with a significant influence of the fimbrial type. The results show that virulence factors like fimbriae may modify the mucosal chemokine response. This mechanism may allow the host to adjust the inflammatory cell infiltrate to fit the infecting strain.
|
|
| 4. |
|
|
| 5. |
- Hammarström, Helena, et al.
(författare)
-
Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies
- 2023
-
Ingår i: Clinical Infectious Diseases. - : University of Chicago Press. - 1058-4838 .- 1537-6591. ; 76:3, s. e1252-e1260
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies.METHODS: This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.RESULTS: Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30.CONCLUSION: In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.
|
|
| 6. |
- Kmezik, Cathleen, 1991, et al.
(författare)
-
A polysaccharide utilization locus from the gut bacterium Dysgonomonas mossii encodes functionally distinct carbohydrate esterases.
- 2021
-
Ingår i: The Journal of biological chemistry. - : Elsevier BV. - 1083-351X .- 0021-9258. ; 296
-
Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota plays a central role in human health by enzymatically degrading dietary fiber and concomitantly excreting short chain fatty acids that are associated with manifold health benefits. The polysaccharide xylan is abundant in dietary fiber but non-carbohydrate decorations hinder efficient cleavage by glycoside hydrolases (GHs) and need to be addressed by carbohydrate esterases (CEs). Enzymes from carbohydrate esterase families 1 and 6 (CE1 & 6) perform key roles in xylan degradation by removing feruloyl and acetate decorations, yet little is known about these enzyme families especially with regards to their diversity in activity. Bacteroidetes bacteria are dominant members of the microbiota and often encode their carbohydrate-active enzymes in multi-gene polysaccharide utilization loci (PULs). Here we present the characterization of three CEs found in a PUL encoded by the gut Bacteroidete Dysgonomonas mossii. We demonstrate that the CEs are functionally distinct, with one highly efficient CE6 acetyl esterase and two CE1 enzymes with feruloyl esterase activities. One multidomain CE1 enzyme contains two CE1 domains: an N-terminal domain feruloyl esterase, and a C-terminal domain with minimal activity on model substrates. We present the structure of the C-terminal CE1 domain with the carbohydrate binding module that bridges the two CE1 domains, as well as a complex of the same protein fragment with methyl ferulate. The investment of D. mossii in producing multiple CEs suggests that improved accessibility of xylan for GHs as well as cleavage of covalent polysaccharide-polysaccharide and lignin-polysaccharide bonds are important enzyme activities in the gut environment.
|
|
| 7. |
- Ohlsson, Pelle, et al.
(författare)
-
Integrated Acoustic Separation, Enrichment, and Microchip Polymerase Chain Reaction Detection of Bacteria from Blood for Rapid Sepsis Diagnostics
- 2016
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:19, s. 9403-9411
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes an integrated microsystem for rapid separation, enrichment, and detection of bacteria from blood, addressing the unmet clinical need for rapid sepsis diagnostics. The blood sample is first processed in an acoustophoresis chip, where red blood cells are focused to the center of the channel by an acoustic standing wave and sequentially removed. The bacteria-containing plasma proceeds to a glass capillary with a localized acoustic standing wave field where the bacteria are trapped onto suspended polystyrene particles. The trapped bacteria are subsequently washed while held in the acoustic trap and released into a polymer microchip containing dried polymerase chain reaction (PCR) reagents, followed by thermocycling for target sequence amplification. The entire process is completed in less than 2 h. Testing with Pseudomonas putida spiked into whole blood revealed a detection limit of 1000 bacteria/mL for this first-generation analysis system. In samples from septic patients, the system was able to detect Escherichia coli in half of the cases identified by blood culture. This indicates that the current system detects bacteria in patient samples in the upper part of the of clinically relevant bacteria concentration range and that a further developed acoustic sample preparation system may open the door for a new and faster automated method to diagnose sepsis.
|
|
| 8. |
|
|
| 9. |
- Otto, Gisela
(författare)
-
Febrile Urinary Tract Infection: P fimbriae, Innate Host Response and Bacteremia
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections (UTI) are among the most common human infections, and febrile UTI with bacteremia the most severe form. The relation between bacteria and host decides disease severity. The dominating uropathogen is Escherichia coli (E. coli). P fimbriae are the virulence factor of E. coli most clearly associated to severe disease. P fimbriated E. coli predominated in bacteremic febrile UTI in both women and men, and carried papDNA sequences of papGIA2 and prsGJ96 adhesin type in both bacteremic and nonbacteremic patients. papGIA2 + E. coli were the major uropathogens in women of all ages, and the major cause of bacteremia in women. prsGJ96 + E. coli were common uropathogens in men, and associated with urinary tract abnormalities. papGIA2+ isolates was the only cause of bacteremia in healthy patients. Bacteremia in patients with host compromise was caused by a mixture of papGIA2+, prsGJ96+ or pap negative isolates. The results emphasise the strong influence of host factors on the selection of uropathogenic E. coli. Febrile UTI was accompanied by a broad and diverse local chemokine response with both CXC and CC chemokines, and by both local and systemic IL-6 responses, as measured in urine and serum. The responses showed therapy-related kinetics. The response magnitudes were associated to bacteremia and disease severity, and influenced by gender and general health. papGIA2+ E. coli were associated to pyelonephritis symptoms, high incidence of bacteremia, and high fever, CRP and higher CCL2/MCP-1 response. Febrile UTI patients with prsGJ96+ isolates had instead more focal symptoms from the lower urinary tract. Systemic IL-6 responses occurred regardless of bacteremia, suggesting that locally produced IL-6 trigger systemic responses. Urine CXCL8/IL-8 was found in all patients and may be used as a marker for UTI, and urine CCL2/MCP-1 for disease severity, correlating to kidney involvement and bacteremia. The results characterise papGIA2+ E. coli as the most virulent strains, with invasive abilities and causing bacteremia, kidney involvement and intense host responses. Seven days of adequate antibiotic therapy was shown to be effective and safe in hospitalised patients with community-acquired febrile UTI, regardless of gender, compromising conditions or bacteremia, and with no difference in clinical and bacteriological outcome compared to 14 days of therapy. Patients with persistence of the original uropathogen developed early clinical infection, whereas all super- or reinfections with gram-positive bacteria were asymptomatic. Bacteremic patients with compromising conditions might need closer observations or longer therapy until further studies. Women had a worse secondary outcome, with lower clinical and bacteriological cure rates, which probably reflect the natural course of UTI in women.
|
|
| 10. |
- Otto, Gisela, et al.
(författare)
-
pap genotype and P fimbrial expression in Escherichia coli causing bacteremic and nonbacteremic febrile urinary tract infection
- 2001
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 32:11, s. 1523-1531
-
Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli strains from patients with febrile urinary tract infections (n=73) were examined for pap genotype and P fimbrial expression in relation to bacteremia and patients' background variables. Most isolates were pap(+) by DNA hybridization (n=51), and 36 were papG(IA2)(+) and 18 prsG(J96)(+) by polymerase chain reaction. The pap and papG genotypes of the infecting strain were shown to vary with host compromise, sex, and age. Bacteremia in noncompromised patients was caused by papG(IA2)(+) strains, but compromised hosts carried a mixture of papG(IA2)(+), prsG(J96)(+), and pap(-) strains. Women of all ages were infected with papG(IA2)(+) strains. Infected men carried prsG(J96)(+) or pap(-) strains and were older, and most had compromising conditions. papG(IA2)(+) strains predominated among patients with medical illness, whereas prsG(J96)(+) strains predominated among patients with urinary tract abnormalities. These findings emphasize the strong influence of host factors on the selection of E. coli strains causing febrile urinary tract infections.
|
|
