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Biomedical subjects

J Andersson

Publications and source records attributed to J Andersson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.

HIV-1 transmission and disease progression is, in general, characterized by initial predominance of macrophage tropic, non-syncytium-inducing strains followed by a switch to T-cell tropic, syncytium-inducing strains. Using sensitive, quantitative kinetic RT-PCR, we examined cytokine regulation of tropism-specific HIV-1 coreceptor expression in PBMCs from HIV-1-seronegative individuals. Proinflammatory (TNF-alpha and IL-12) and type 1 cytokines (IFN-gamma and IL-2) significantly upregulated CCR5 (wt allele) mRNA expression in CCR5 homozygous wild-type (wt/wt) and heterozygous individuals (wt/del) (P < 0.02). CCR5 (wt) mRNA expression in unstimulated PBMCs was significantly increased in wt/wt individuals compared to that of wt/del individuals (P < 0.01). In wt/del individuals, del CCR5 mRNA was expressed at 10-fold greater levels than wt CCR5 mRNA in unstimulated PBMCs from the same individual. Flow cytometry confirmed that upregulated CCR5 mRNA following type 1 cytokine stimulation leads to increased cell surface expression of CCR5 protein. The type 2 cytokine IL-10 downregulated both CCR5 mRNA and protein expression in wt/wt and wt/del individuals. Proinflammatory, type 1, and type 2 cytokines significantly increased CXCR4 mRNA expression in wt/wt, wt/del, and del/del CCR5 genotypes (P < 0.02). These results suggest that changes in the cytokine milieu influence chemokine receptor expression and may explain emergence of tropism-specific strains facilitating HIV transmission and disease progression.

Base Sequence↗
PubMed1999

The roles of preB and B cell receptors in the stepwise allelic exclusion of mouse IgH and L chain gene loci.

Membrane-bound preBCR of wild-type mice, and probably also preBCR-like V(preB) muH chain complexes in lambda5-deficient mice, signal allelic exclusion so that < 0.1% of all preB-II cells and all subsequent B lineage cells express two muH chains on their surface. On the other hand a large number of muH chains which are originally generated at the transition of preB-I to preB-II cells cannot pair with surrogate L chains, cannot form a preBCR on the surface and, hence, allow two H chain alleles to be productively rearranged in one B-lineage cell. By contrast membrane-bound BCR on immature B cells does not signal allelic or isotypic exclusion Of Ig kappaL and lambdaL chain gene loci. This allows the rearrangement machinery to remain active, and secondary L chain rearrangements on one kappaL chain allele are frequently observed. Rapid selection of fitting H/L chain pairs, forming BCR on the surface, allows B-lineage cells to enter the mature B cell pool where the rearrangement machinery is shut off, securing allelic exclusion of L chain loci in most B cells.

Alleles↗
PubMed1999

Mutations affecting either generation or survival of cells influence the pool size of mature B cells.

The mature B cell compartment of MHC class II-deficient B6 I-Aalpha(-/-) and the btk-defective CBA/N mouse strain is 4- to 5-fold smaller than in wild-type B6 mice. The defect in B6 I-Aalpha(-/-) mice is intrinsic to B cells and due to a 4- to 5-fold reduced lifespan, which however can be normalized by an I-Ealpha(d) transgene, but only when expressed early during B cell development. The reduced number of mature B cells in the btk-defective CBA/N mouse is due to a 4- to 5-fold lower number of immature splenic B cells entering the mature compartment. The combined defects of reduced lifespan and impaired generation in double mutant mice result in a severe deficiency in the mature B cell pool.

Animals↗
PubMed1999

Four of five RAG-expressing JCkappa-/- small pre-BII cells have no L chain gene rearrangements: detection by high-efficiency single cell PCR.

Single cell PCR assays have been further developed that detect over 80% of all VkappaJkappa, VkappaRS, and VlambdaJlambda rearrangements at efficiencies between 70% and 90%. These IgL chain gene rearrangement assays were used with small pre-BII cells that develop in comparably high numbers in the bone marrow of wild-type, Ckappa-deficient, and JCkappa-deficient homozygous and heterozygous mice. In all of these mice, only 15%-25% of all small pre-BII cells carry VlambdaJlambda rearrangements. These results confirm that lambdaL chain gene rearrangements occur independently of kappaL chain gene rearrangement and expression. They also show that a large part of the small pre-BII cells that express the rearrangement machinery can develop without IgL chain gene rearrangements.

Animals↗
PubMed1999

Frequencies of multiple IgL chain gene rearrangements in single normal or kappaL chain-deficient B lineage cells.

PCR analyses of the kappaL chain locus in single B-lineage cells of wild-type, Ckappa-, or JCkappa-deficient homozygous or heterozygous mice often detect multiple in- and out-of-frame rearrangements at the kappaL and lambdaL loci. They are most frequent in small pre-BII cells and equally so in wild-type and kappaL chain-deficient cells. Hence, kappaL chain production appears not to inhibit secondary rearrangements. Around 20% of all small preBII cells express IgL chains in their cytoplasm. Cells with a first productive rearrangement on one allele are favored to enter the immature B cell compartment. Thus, allelic exclusion might be secured by control of accessibility of IgL chain loci for rearrangement and by rapid selection of cells with a fitting over those with a nonfitting IgL chain.

Alleles↗
PubMed1999

High-dose acyclovir prophylaxis reduces cytomegalovirus disease in liver transplant patients.

Cytomegalovirus (CMV) is still a major pathogen in liver transplantation (LTX). The clinical efficacy of prophylactic high-dose acyclovir therapy (800 mg qid) was assessed for the prevention of CMV infection and disease in liver recipients. Fifty-five patients were enrolled in a prospective, randomised, double-blind and placebo-controlled trial; 28 on acyclovir vs. 27 on placebo. The therapy was given for 12 weeks. The patients were followed for 24 weeks. CMV infection was diagnosed in 60% (16 on acyclovir, 17 on placebo) and CMV disease developed in 38% (7 on acyclovir, 14 on placebo) of the patients. The total mortality was 27% (6 on acyclovir, 10 on placebo). Acyclovir delayed 32% of the CMV infections and prevented 59% of the CMV disease cases which occurred in the placebo cohort. The time to CMV disease was significantly prolonged in patients on acyclovir as compared to patients on placebo (P=0.013). Adverse events included neurotoxicity which occurred in 5 cases in the acyclovir, but none in the placebo arm, and nephrotoxicity which was detected in 6 patients in the acyclovir and 5 in the placebo arm, respectively. We conclude that acyclovir prophylaxis significantly reduced the incidence of CMV disease, and delayed the onset of CMV infection in liver transplant patients.

Acyclovir↗
PubMed1999

The distinct role of CD4+ and CD8+ T-cells during the anti-tumour effects of targeted superantigens.

To target T-cells to the tumour area we created a recombinant protein of the bacterial superantigen (SAg) Staphylococcal enterotoxin A (SEA) and the Fab-fragment of a tumour-reactive antibody. This antibody-targeted SAg immunotherapy therapy has been shown to be highly efficient, eliminating > 95% of the pulmonary metastasis in mice carrying established melanoma micrometastases. Earlier studies demonstrated that elimination of the C215-expressing B16-melanoma lung metastasis was dependent on interferon (IFN)-gamma release and expression of perforin. In the present study, therapeutic effector functions were analysed both locally at the tumour site and systemically in the spleen. In order to elucidate the role of each T-cell subset during Fab-SEA therapy, CD4 knock-out (KO) and CD8 KO mice were used. Tumour size reduction was statistically significant in Fab-SEA-based tumour therapy in both types of T-cell-deficient mice compared to wild-type mice. CD4 KO mice displayed a drastic reduction in the number of tumour-infiltrating macrophages and CD8+ T-cells. Therapy-induced accumulation of perforin-containing cells at the tumour site was significantly impaired in CD8 KO mice, and marginally in CD4 KO mice. Moreover, CD4 KO mice failed to produce substantial amounts of the tumour suppressive cytokine IFN-gamma. This is in sharp contrast to normal mice where a massive local release was recorded. CD8 KO mice displayed a spontaneous production of interleukin (IL)-4 and IL-10 locally in the tumour. Neither normal nor CD4 KO mice produced detectable levels of these Th-2-associated cytokines. The high level of IL-10 was demonstrated to inhibit Fab-SEA tumour therapy, since the therapeutic efficacy was significantly higher in IL-10 KO mice. These results illustrate the importance of a finely tuned cellular collaboration to regulate the various phases of an efficient anti-tumour immune response.

Animals↗
PubMed1999

A speechreading expert: the case of MM.

The present case study of MM, who acquired both sign language and spoken language in her early preschool years-and then reached the normal milestones of development in each language--revealed that her speechreading expertise is associated with cognitive functions such as high working memory capacity and phonological skills. Her cognitive profile is in accord with previous case studies of extremely good speechreading skill. MM's enhanced right prefrontal/frontal cerebral blood flow activation during speechreading seems to be indicative of efficient visual scanning, but it is also possibly due to her strategy for phonological decoding of visual speech.

Adult↗
PubMed1999

Anti-inflammatory effects of a new tumour necrosis factor-alpha (TNF-alpha) inhibitor (CNI-1493) in collagen-induced arthritis (CIA) in rats.

A recently developed compound, a multivalent guanylhydrazone (CNI-1493) that inhibits TNF-alpha production by suppressing TNF-alpha translational efficiency, was administered in an experimental model of collagen type II-induced arthritis in DA rats. CNI-1493 was injected daily intraperitoneally either before the onset of arthritis or after the establishment of clinical disease. Prophylactic treatment with CNI-1493 significantly prevented or delayed the onset and suppressed the severity of arthritis in a dose-dependent manner. Therapeutic intervention with CNI-1493 in established joint disease also resulted in a significant reduction of clinical signs of arthritis in treated animals. No severe side-effects were noted when animals were treated with daily CNI-1493 doses up to 5 mg/kg. An immunohistochemical study was performed which demonstrated that CNI-1493 led to a reduced expression of TNF-alpha at the site of disease activity. Thus, CNI-1493 with documented inhibitory effects on TNF-alpha synthesis, has proven successful in ameliorating the course of arthritis in CIA. We believe that the use of a compound such as CNI-1493 with a defined mode of action provides a useful tool for dissecting and understanding important pathogenic mechanisms operating in the development of chronic arthritis.

Animals↗
PubMed1999

Invasive group A streptococcal infections: T1M1 isolates expressing pyrogenic exotoxins A and B in combination with selective lack of toxin-neutralizing antibodies are associated with increased risk of streptococcal toxic shock syndrome.

Analysis of 132 group A streptococcal (GAS) isolates from 151 invasive episodes, including streptococcal toxic shock syndrome (STSS), from 1983 to 1995 showed great genetic variation by use of T serotyping in combination with restriction fragment length polymorphism. In contrast, genetically homogenous T1M1 isolates appeared in epidemic patterns with significantly increased risk of STSS. The speA gene, with the allelic variants speA2 and speA3 carried by the T1M1 and T3M3 serotypes, respectively, was strongly associated with STSS. Infection with a GAS isolate carrying speA, alcohol abuse, and malignancy recently treated with cytostatic drugs were factors independently related to STSS. Neutralization of SpeA lymphocyte mitogenicity was totally absent in sera from patients with STSS and low in sera from persons with uncomplicated bacteremia compared with levels in sera from uncomplicated erysipelas. Neutralization of SpeB was significantly lower in sera of patients with STSS than in sera from persons with bacteremia or erysipelas.

Adult↗
PubMed1999

Interferon gamma (IFN-gamma) deficiency in generalized Epstein-Barr virus infection with interstitial lymphoid and granulomatous pneumonia, focal cerebral lesions, and genital ulcers: remission following IFN-gamma substitution therapy.

A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.

Adult↗
PubMed1999

Renal transplantation in patients with urinary diversion: a case-control study.

BACKGROUND: Renal transplantation in Sweden in patients with ileal conduits or continent reservoirs was investigated in order to compare the outcome with regard to graft and patient survival as compared to controls. METHODS: Patient data from the four transplantation centres in Sweden were collected on: treatment prior to transplantation, time needed for the operative procedure, and postoperative care and outcome in terms of renal function as well as graft and patient survival at 1 and 5 years. The pattern of urinary tract infection was also investigated. Each case with urinary diversion was matched with two non-diabetic controls. RESULTS: Ten male and 12 female cases were found who had received 27 grafts between 1982 and 1996. Five patients had a Kock reservoir and 17 had a Bricker conduit. The time needed for the transplant procedure was significantly longer in the case group. After matching the case group with 54 controls, we found that the renal function was similar in both groups. Graft and patient survival was similar in both groups, over 90% after 1 year. Graft survival was about 70% after 5 years. Postoperative surgical complications in the case group were only seen in a few cases. The pattern of bacteria causing urinary tract infection was slightly different among the patients with ileal conduits or continent reservoirs. CONCLUSION: Patients with ileal conduits or continent reservoirs have similar graft and patient survival rates as the general kidney transplant population. The presence of constant bacteriuria did not adversely affect survival. Prophylactic antibiotic treatment seems not to be warranted. There appears to be no indication for native nephrectomy, except in selected cases. The study did not show any advantage with regard to continent reservoirs vs ileal conduits.

Adolescent↗
PubMed1999

Titanium is a highly thrombogenic biomaterial: possible implications for osteogenesis.

Titanium has superior osteointegrating properties compared to other biomaterials. The mechanism for this is unknown. During the initial phase of bone implantation the biomaterial comes into direct contact with whole blood. In this study we use a newly developed in vitro chamber model to compare different commonly used biomaterials in contact with whole blood. These materials were selected with respect to their different osteointegrating properties in order to correlate these properties with the response to whole blood. In the presence of 3 IU/ml of heparin only titanium induced macroscopic clotting. This was reflected by the generation of thrombin-antithrombin which was much increased in blood in contact with titanium compared with steel and PVC. The coagulation activation caused by titanium was triggered by the intrinsic pathway because the generation of FXIIa-AT/C1 esterase inhibitor paralleled that of thrombin-antithrombin, and both thrombin-antithrombin complex and FXIIa-AT/C1 esterase inhibitor generation were abrogated by corn trypsin inhibitor, which is a specific inhibitor of FXIIa. The binding of platelets was increased on the titanium surface compared to the other biomaterial surfaces and the state of platelet activation was much more pronounced as reflected by the levels of beta-thromboglobulin and PDGF. This study indicates that titanium is unsuitable as a biomaterial in devices which are in direct contact with blood for a prolonged period. Furthermore, PDGF and other alpha-granule proteins e.g. TGF-beta, are known to be potent promotors of osteogenesis which suggests that the pronounced thrombogenic properties of titanium might contribute to the good osteointegrating properties.

Blood Coagulation↗