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Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 271 records · Page 15Linked to original sources
PubMed1998

CTLA-4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are T-cell mediated organ-specific autoimmune disorders with a genetic predisposition. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule is the predominant receptor for B7 on activated T cells and represents a negative regulator for T-cell function. Since the CTLA-4-guanine at position 49 of exon 1 is associated with susceptibility to GD as well as to HT and IDDM, we investigated a recently detected cytosine/thymine substitution at position -318 within the CTLA-4 promoter region in patients with GD and HT. 125 patients with GD were significantly more often homozygous for cytosine (86% vs. 73% in controls, P=0.006) and less frequently heterozygous for cytosine and thymine (14% vs. 27%, P=0.008). In 64 patients with HT, the distribution was similar but not significant (81% homozygous for cytosine and 16% heterozygous). When correlating the promoter and the exon 1 polymorphism we found the strongest linkage between thymine (promoter) and adenine (exon 1). In conclusion, a promoter variant of the CTLA-4 gene represents an additional risk marker for GD and HT, but their predisposition is linked to the exon 1 alleles.

Abatacept↗
PubMed1998

CD1 presents antigens from a gram-negative bacterium, Haemophilus influenzae type B.

Human CD1 is a family of nonpolymorphic major histocompatibility complex class I-like molecules capable of presenting mycobacterial lipids, including lipoarabinomannan (LAM), to double-negative (DN; CD4(-) CD8(-)) as well as CD8(+) T cells. Structural similarities between LAM and the capsular polysaccharides of gram-negative bacteria led us to consider the latter as candidate CD1 ligands. We derived two CD1-restricted DN T-cell populations which proliferated to Haemophilus influenzae type b (Hib) antigen. One T-cell population also proliferated to proteinase K-treated Hib antigen, suggesting that it recognized a nonpeptide. Our work thus expands the universe of T cell antigens to include nonpeptides distinct from mycobacterial lipids and suggests a potential role for CD1-restricted T cells in immunity to Hib.

Antigen Presentation↗
PubMed1998

Contact with thymic epithelial cells as a prerequisite for cytokine-enhanced human immunodeficiency virus type 1 replication in thymocytes.

We report here that human immunodeficiency virus type 1 (HIV-1)-infected human thymocytes, in the absence of any exogenous stimulus but cocultivated with autologous thymic epithelial cells (TEC), obtained shortly (3 days) after thymus excision produce a high and sustained level of HIV-1 particles. The levels and kinetics of HIV-1 replication were similar for seven distinct viral strains irrespective of their phenotypes and genotypes. Contact of thymocytes with TEC is a critical requirement for optimal viral replication. Rather than an inductive signal resulting from the contact itself, soluble factors produced in the mixed culture are responsible for this effect. Specifically, the synergistic effects of tumor necrosis factor, interleukin-1 (IL-1), IL-6, and granulocyte-macrophage colony-stimulating factor may account by themselves for the high level of HIV-1 replication in thymocytes observed in mixed cultures. In conclusion, the microenvironment generated by TEC-thymocyte interaction might greatly favor optimal HIV-1 replication in the thymus.

Cell Communication↗
PubMed1998

Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response.

The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease. The alveolar macrophage (AM) is a potential target cell for the pathogen and may contribute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumoniae and AM from 12 healthy volunteers. Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced productive infection in the AM. Inclusions containing replicating pathogens could be maintained for up to 120 h. Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C. pneumoniae pneumonia. AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8. ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C. pneumoniae pneumonia.

Adult↗
PubMed1998

Withdrawing attention at little or no cost: detection and discrimination tasks.

We used a concurrent-task paradigm to investigate the attentional cost of simple visual tasks. As in earlier studies, we found that detecting a unique orientation in an array of oriented elements ("pop-out") carries little or no attentional cost. Surprisingly, this is true at all levels of performance and holds even when pop-out is barely discriminable. We discuss this finding in the context of our previous report that the attentional cost of stimulus detection is strongly influenced by the presence and nature of other stimuli in the display (Braun, 1994b). For discrimination tasks, we obtained a similarly mixed outcome: Discrimination of letter shape carried a high attentional cost whereas discrimination of color and orientation did not. Taken together, these findings lead us to modify our earlier position on the attentional costs of detection and discrimination tasks (Sagi & Julesz, 1985). We now believe that observers enjoy a significant degree of "ambient" visual awareness outside the focus of attention, permitting them to both detect and discriminate certain visual information. We hypothesize that the information in question is selected by a competition for saliency at the level of early vision.

Adult↗
PubMed1998

Use of dynamic magnetic resonance imaging to detect sacroiliitis in HLA-B27 positive and negative children with juvenile arthritides.

OBJECTIVE: Involvement of the sacroiliac (SI) joints is a hallmark of the spondyloarthropathies (SpA), especially, in early and later stages of ankylosing spondylitis in adults. The significance of sacroiliitis in juvenile SpA is less clear and the diagnosis of juvenile SpA is difficult due to the mostly nonspecific or absent history of back pain in children and the time delay associated with the diagnosis of sacroiliitis by conventional radiographs. Our aim was to evaluate dynamic magnetic resonance imaging (MRI) of the SI joints in children and to assess the frequency and the determinants of SI joint involvement in juvenile SpA and other juvenile arthritides. METHODS: Clinical examinations and dynamic MRI were performed in 130 children < 16 years of age with joint complaints, 100 with probable SpA, and 30 controls. The degree of back pain was assessed by a visual analog scale (VAS) (0 = no pain, 10 = very severe pain). The following groups were defined before MRI investigation according to modified European Spondylarthropathy Study Group (ESSG) criteria for SpA: Group 1: undifferentiated SpA (uSpA, n = 41, 88% B27+); Group 2: differentiated SpA (n = 29, 97% B27+), comprising reactive arthritis (n = 16), ankylosing spondylitis (n = 9), psoriatic arthritis (n = 3), and arthritis in inflammatory bowel disease (n = 1); Group 3: patients with no signs of SpA other than oligoarthritis, here named juvenile chronic arthritis (JCA) II (n = 30, 93% B27+); Group 4: HLA-B27+ controls without arthritis (n = 12); and Group 5: HLA-B27-controls with various other non-SpA diagnoses (n = 18). MRI was evaluated according to published criteria allowing for differentiation between acute and chronic changes in SI joints. RESULTS: Acute sacroiliitis without chronic changes could only be detected by dynamic MRI: in 17 patients (11 in Group 1, 3 in Group 2, 3 in Group 3) together in 14/70 (20%) patients with SpA. All these 17 patients had normal pelvic radiographs. Using MRI acute and/or chronic sacroiliitis were found in 35 patients: 17/41 in Group 1 (41%), 15/29 in Group 2 (52%), and 3/30 (10%) patients in Group 3, but in no patients in Groups 4 and 5. Chronic SI joint changes > grade 1 were detected by MRI in 18/70 patients with SpA (25.7%). In comparison, radiographic changes > grade 1 were less often detected in 14/70 patients with SpA (20%) or 23/210 SI joints examined (11 %), compared to 29/210 SI joints found in the MRI examinations (14%) (p = 0.05). Among the 70 patients with SpA, those with MRI diagnosis of acute sacroiliitis had a significantly longer disease duration (62+/-34 vs 28+/-16 months; p = 0.01) and higher C-reactive protein (12+/-12 vs 9+/-14; p = 0.01), and also reported more back pain on VAS (4.3+/-3.6 vs 1.2+/-2.2; p = 0.001) than those without sacroiliitis. CONCLUSION: Dynamic MRI and MRI are useful to detect acute and chronic sacroiliitis in children. The main advantages in comparison with conventional radiographs are the ability to detect acute changes in the SI joints, the higher sensitivity to detect chronic changes, and clearly, the lack of radiation exposure; while the disadvantages are the high costs and the duration of the procedure. Sacroiliitis is fairly common in juvenile SpA and seems to be associated with disease intensity and duration.

Adolescent↗
PubMed1998

Increased frequency of Sjögren's syndrome in patients with spondyloarthropathy.

OBJECTIVE: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). METHODS: Patients with SpA with inflammatory back pain and/or peripheral arthritis presenting to the university outpatient clinic were diagnosed as AS (n = 40) and uSpA (n = 65) according to established criteria. Patients with SpA with sicca symptoms and/or positive antinuclear antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or sialography. To assess sicca symptoms in this cohort systematically we mailed a validated questionnaire with 6 questions on dryness of eyes and mouth to all 105 SpA patients and 150 healthy controls, a positive answer to > or = 3 questions was taken as suggestive of SS. There was no significant difference in baseline characteristics between patients and controls. RESULTS: In 8/105 SpA patients (5 uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS; thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients responding to the questionnaire (80%), 10 gave a positive answer to > or = 3 questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7, 95% CI 2.3-32.5, p < 0.01). CONCLUSION: The data suggest increased prevalence of sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a secondary SS in a variety of inflammatory diseases suggests that salivary gland involvement in these conditions results from as yet unidentified shared pathogenic mechanisms resulting in nonspecific inflammation in this location.

Adult↗
PubMed1998

[Direct ileum pouch-anal anastomosis in ulcerative colitis: function and complications after stapler technique].

Stapled ileal pouch-anal anastomosis after proctocolectomy enables a continence preserving reconstruction. We assessed complications and functional outcome after ileoanal pouch-anastomosis in 86 consecutive patients with ulcerative colitis. There was no postoperative mortality. 2 patients required permanent ileostomy and pouch excision for manifestation of unsuspected Crohn's disease. Major postoperative complications consisted of pelvic sepsis (n = 2), anastomotic leakage (n = 4), bleeding (n = 1), pancreatitis (n = 3) and peritonitis (n = 1). Both frequencies of bowel movements and degree of continence improved with time. Two years after take down of the deviation ileostomy frequency of bowel movements was 5,6 [2]/die. At this time no patient complained of major incontinence. Minor incontinence was reported with 9% and 14% during day-time and night-time respectively. It is concluded that direct stapled ileal pouch-anal anastomosis is a safe procedure with excellent functional results for patients with ulcerative colitis.

Adolescent↗
PubMed1998

[Use of PGF2alpha and GnRH for estrus synchronization in cattle].

Estrus detection has a tremendous impact on the reproductive efficiency in dairy farms. Recently the systematic use of hormones for synchronization of estrus and ovulation has been propagated. These programs are designed to facilitate estrus detection and/or increase its efficiency. Prostaglandin programs are used to improve estrus detection and reproductive management in dairy operations. All cows are treated up to three times in weekly or biweekly intervals at the end of the voluntary waiting period. This should lead to groups of cows in estrus within two to four days after PG treatment. Since PG programs cannot completely eliminate the need for estrus detection procedures for fixed time artificial insemination (AI) were developed. Fixed time AI not only requires control of the luteal phase of the cow but also synchronization of the follicular development. Treatment with GnRH will induce a new follicular wave and provide a dominant follicle in a defined growth phase at the time of PG administration seven days later. A second injection of GnRH given 48 hours after PG results in ovulation approximately 24 to 32 hours after GnRH (OvSynch-procedure). The pros and cons of hormone programs in dairy farming are discussed in the light of field trials and experiments performed in our department.

Animals↗
PubMed1998

Short-term follow up of the Ross operation in children.

BACKGROUND AND AIMS OF THE STUDY: Aortic valve disease in the pediatric population poses special problems to surgeons and cardiologists. The pulmonary autograft has proven to be a good alternative for aortic valve replacement and left ventricular outflow tract (LVOT) reconstruction in this special group. METHODS: Forty-one children (mean age 10.0 +/- 4.8 (SD) years; range: 35 days to 18.8 years) underwent aortic root replacement with a pulmonary autograft between February 1994 and April 1998. Twenty-one patients (51%) had previous cardiac surgery; seven (17%) had balloon valvulotomy. Aortic root replacement was combined with other techniques for various disorders, including tunnel LVOT obstruction, ventricular septal defect (VSD)-aortic insufficiency complex, neoaortic insufficiency following arterial switch procedure, and subvalvular stenosis following correction of type B interruption of the aortic arch (IAA) with VSD (IAA-B/VSD). RESULTS: The mean follow up was 1.7 +/- 1.0 years (range 44 days to 4.1 years). Total follow up time was 67.8 patient-years. Two patients, both after repair of interrupted aortic arch, died intraoperatively (4.9%). There was no late mortality. Two patients were reoperated on (5.1%), one for autograft insufficiency due to cuspal perforation and one for right ventricular outflow tract stenosis at the distal anastomosis. Thirty-eight patients (97%) are currently in NYHA class I; one child with a preoperatively poor left ventricular function did not improve and is in class II. At the latest echocardiographic follow up, neoaortic regurgitation was absent in 19% of patients, trivial in 69% and mild in 11%. Homograft insufficiency was absent in 64%, trivial in 31% and mild in 6%. All mean gradients for both autograft and homograft were < 15 mmHg. CONCLUSIONS: The Ross operation can be performed with good results in infants and children with different forms of LVOT obstruction and aortic insufficiency, though aortic stenosis following IAA-B/VSD repair poses a surgically difficult problem.

Adolescent↗
PubMed1998

[Incidence of bacterial pneumonia in HIV-positive patients treated with preventive co-trimoxazole or pentamidine].

BACKGROUND: Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown. PATIENTS AND METHODS: We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk. RESULTS: We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias. CONCLUSION: There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Value of MRI, CT and findings in staging of gynecologic malignancies].

PURPOSE: The present study was designed to compare the value of MRI, CT and clinical examination in local tumor staging of gynaecologic malignancies. PATIENTS AND METHODS: 99 patients with clinically suspected carcinoma of the cervix uteri, ovarian carcinoma or tumor recurrence after gynaecologic cancer underwent all three staging modalities. Furthermore CT and MRI were compared in detecting lymph node metastasis and peritoneal implants. RESULTS: MRI was superior to CT and clinical staging in local tumor staging with an accuracy of 77% for cervical carcinoma and of 88% for recurrent tumors, whereas CT achieved an accuracy of 65% and 55% and clinical staging 60% and 63% accuracy for carcinoma of the cervix and recurrent cancer. Especially for local staging of these two tumor entities MRI is very useful. MRI and CT reached comparable results in the detection of ovarian tumors with an accuracy of 73% for MRI and 69% for CI. Both imaging modalities also showed equal results in the detection of lymph node metastasis, so that primary the cost saving use of CT tumor staging for ovarian lesions and lymph node metastasis should be favoured.

Female↗
PubMed1997

Transcription and activity of 5-fluorouracil converting enzymes in fluoropyrimidine resistance in colon cancer in vitro.

Cellular resistance to 5-fluorouracil (5-FU) is not completely understood. Since 5-FU shares the pyrimidine pathway with the physiological pyrimidines, we investigated the relationship between fluoropyrimidine metabolism, nucleic acid uptake and cytotoxicity of 5-FU in eight colon tumour cell lines including 5-FU-resistant subclones. The cytotoxicity of 5-FU was increased up to 423-fold when the anabolites 5-fluorouridine (FUrd), 5-fluorodeoxyuridine (FdUrd), and 5-fluorodeoxyuridine monophosphate (FdUMP) were compared with the parent drug in vitro. The enzymes uridine phosphorylase and thymidine phosphorylase were predictive for the cytotoxicity of 5-FU in 5/7 cell lines. Inhibition of uridine phosphorylase and thymidine phosphorylase by antisense strategies effectively antagonised 5-FU, abolishing 84% and 79% of its toxicity. The importance of thymidine phosphorylase was supported by a highly restricted enzyme activity in 5-FU-resistant cells. In 5-FU naive cells, a stimulating effect of 5-FU on thymidylate synthase mRNA and ribonucleotide reductase mRNA expression was observed. In these cells, antisense oligonucleotides to ribonucleotide reductase significantly reduced cell growth. Downregulation of ribonucleotide reductase mRNA in 5-FU-resistant subclones suggests different mechanisms in primary and secondary resistance to 5-FU. Most of the intracellular 5-FU was selectively incorporated into RNA (range: 45-91%) and generally spared DNA (range: 0.2-11%). In synthesising our data, we conclude that drug resistance could be overwhelmed through bypassing limiting steps in the activation of 5-FU. In the majority of colonic tumours, the activity of uridine phosphorylase and thymidine phosphorylase may have prognostic relevance for the cytotoxicity of 5-FU in vitro.

Antimetabolites, Antineoplastic↗
PubMed1997

A single nonamer from the Yersinia 60-kDa heat shock protein is the target of HLA-B27-restricted CTL response in Yersinia-induced reactive arthritis.

The reason for the high association of HLA-B27 with diseases such as ankylosing spondylitis and reactive arthritis is not clear. In reactive arthritis, the triggering bacteria are known, thus allowing investigation of their interaction with HLA-B27. CTL lines derived from five patients with Yersinia-induced reactive arthritis were raised by repeated stimulation in vitro with either Yersinia-infected autologous macrophages (four patients) or pooled peptides (three patients) having the HLA-B27-binding motif. The peptides were derived from five Yersinia proteins and from the chlamydial 57-kDa heat shock protein (hsp). Cytotoxicity of T cell lines was then tested against these peptides. Lytic activity was obtained with T cells stimulated with viable Yersinia or pooled peptides. Targets successfully used for lysis were cells pulsed with peptides from the Yersinia 60-kDa hsp, but not cells pulsed with peptides from other Yersinia proteins or the chlamydial hsp. T cell lines raised with 60-kDa peptides also lysed targets infected with Yersinia. Most interestingly, all three CTL lines tested (one raised with Yersinia; two with pool of peptides) recognized only one single peptide (321-329) of seven tested from the Yersinia hsp60. Cytotoxicity occurred only when target cells were matched for HLA-B27. This identification of an immunogenic peptide derived from an arthritogenic bacterium and presented by HLA-B27 opens the way for future investigation of the role of T cells specific for this peptide or cross-reacting peptides, in the immunopathology of HLA-B27-associated diseases.

Arthritis, Infectious↗