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Biomedical subjects

B Schiller

Publications and source records attributed to B Schiller.

At least 19 recordsLinked to original sources
PubMed1999

Indicators of dysautonomia in severe Guillain-Barré syndrome.

This study sought to establish quantitative criteria for dysautonomia in artificially ventilated patients with Guillain-Barré syndrome (GBS). Such criteria would help to identify patients at risk for cardiovascular complications. This retrospective controlled clinical study compared hourly cardiovascular monitoring data from 36 successive, artificially ventilated GBS patients with that from 11 artificially ventilated control patients with myasthenia. Tolerance limits for daily means, extremes, and variations in heart rate (HR) and blood pressure (BP) were estimated from the most abnormal subgroups of the treatment days of our control patients. These exceeded previously suggested arbitrary cutoff values for dysautonomia. The range in systolic BP was increased in 27 GBS patients, despite an upper limit of normal (85 mmHg) that was double the value suggested in previous work. All 16 patients with mean systolic BP above 165 mmHg also had persistent tachycardia (mean HR > 125 bpm), or were treated with beta-blockers. This pattern of sympathetic hyperactivity was combined with probable vagal hyperactivity (bradycardia < 48 bpm) in 6 patients. Hypotension (minimal systolic BP < 85 mmHg) and unprovoked bradycardia indicated sympathetic hypoactivity in 3 patients. Except in one patient who suffered from asystole on his first day on the ICU, all episodes of bradycardia were preceded by increased daily systolic BP variation (> 85 mmHg), which thus proved to be a sensitive and prognostically valuable indicator of dysautonomia in GBS.

Autonomic Nervous System Diseases↗
PubMed1999

Inflammatory parameters and soluble cell adhesion molecules in Swedish children with Kawasaki disease: relationship to cardiac lesions and intravenous immunoglobulin treatment.

The possible use of inflammatory parameters as a predictor of coronary artery lesions (CAL) and the effect of intravenous immunoglobulin (IVIG) treatment in 30 Swedish children with acute Kawasaki disease were investigated. All the patients were treated with IVIG (2 g/kg) and seven of them had CAL. Ten febrile children, hospitalized for treatment of severe infection, and 15 healthy children served as controls. The levels of soluble E-selectin and soluble intercellular adhesion molecule (ICAM)-1 in the Kawasaki patients were elevated in comparison to healthy, but not in comparison to febrile controls. Paired analysis of our patients before and after IVIG therapy during acute disease revealed lowered levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1. We found no statistically significant relationships among any of these parameters as a possible predictor of CAL, but three patients with cardiac sequelae demonstrated high values for these inflammatory parameters. These findings may reflect endothelial activation in connection with vasculitis, and the anti-inflammatory effect of IVIG treatment lowering cytokine levels and subsequently decreasing the expression and shedding of adhesion molecules. In conclusion, we were unable to identify a predictor of CAL in the acute phase. The patients had higher levels of soluble E-selectin and soluble ICAM-1 than did afebrile controls, but not febrile controls. The patients' levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1 were decreased after 1-2d of IVIG treatment.

C-Reactive Protein↗
PubMed1998

Inhibition of complement regulation is key to the pathogenesis of active Heymann nephritis.

Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface.

Animals↗
PubMed1998

Characterization of the T-cell receptor V-beta repertoire in Kawasaki disease.

Kawasaki disease (KD) is a paediatric multisystem necrotizing vasculitis constituting the most frequent cause of acquired heart disease in childhood. Conflicting data have been reported regarding expanded T-cell populations using particular T-cell receptor (TCR) beta-chain variable (BV) gene segments, suggesting either a superantigen- or a conventional antigen-mediated immune response in this disease. In order to further investigate the role of T lymphocytes, cells were stained with an extensive panel of 21 different TCRBV specific monoclonal antibodies (MoAbs) covering almost 70% of all T-cells. Flow cytometry was employed to analyse the expression of the TCRBV repertoire in the CD4+ and CD8+ subsets separately, and of activation markers, in freshly isolated peripheral blood lymphocytes of 25 Kawasaki disease patients during the acute and convalescent phases of the disease. No abnormal usage of any TCRBV family was found, neither acutely nor during convalescence, compared with a control group of healthy children. However, a significant increase in interleukin-2 receptor (IL-2R)-expressing T lymphocytes restricted to the CD4+ subset was observed in KD patients. Our data confirm a strong immune activation in KD that might be of importance in the pathogenesis of the disease.

Child↗
PubMed1998

Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.

We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present.

Adult↗
PubMed1997

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines.

BACKGROUND: The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. METHODS: We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. RESULTS: The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.

Animals↗
PubMed1996

Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule.

The avidity of integrin adhesion receptors for extracellular ligands is subject to dynamic regulation by intracellular programs that have yet to be elucidated. We describe here a protein, cytohesin-1, which specifically interacts with the intracellular portion of the integrin beta 2 chain (CD18). The molecule shows homology to the yeast SEC7 gene product and bears a pleckstrin homology (PH) domain. Overexpression of either the full-length cytohesin-1 or the SEC7 domain induces beta 2 integrin-dependent binding of Jurkat cells to ICAM-1, whereas expression of the isolated cytohesin-1 PH domain inhibits T cell receptor-stimulated adhesion. Similar inhibition is not exhibited by PH domains taken from other proteins, showing that the interaction is specific and that individual PH domains are capable of discriminating between alternative targets.

Amino Acid Sequence↗
PubMed1996

Experimental glomerulosclerosis: Defektheilung of the kidney.

Research in the role of cytokines in experimental glomerulonephritis has increased our understanding of the mechanisms that may be involved in the development of progressive renal disease. Glomerulosclerosis, the final common pathway in a variety of underlying kidney diseases, is characterized by increased extracellular matrix formation and cell proliferation. Transforming growth factor-beta (TGF-beta) and monocyte chemoattractant protein-1 (MCP-1) have been identified in animal models as mediators in the processes that follow renal injury. There is evidence of similar events occurring in other fibrotic disorders, suggesting that there is a common generic pathway of fibrosis. This review summarizes our knowledge of TGF-beta and MCP-1 in experimental kidney disease and compares these results with mechanisms described in other organs. We propose that glomerulosclerosis represents Defektheilung (healing by secondary intention) of the kidney after various injuries. The growing knowledge of the mechanisms involved will help advance future therapeutic interventions by directing the healing process toward primary healing.

Animals↗
PubMed1996

Effects of osmotic solutes on fibronectin mRNA expression in rat peritoneal mesothelial cells.

Hypertonic glucose in a peritoneal dialysate may modulate cell metabolism in the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). To examine the effects of high glucose concentration and hyperosmolarity, rat mesothelial cells were cultured for 3 or 6 days in media containing either 5, 25 or 50 mM glucose containing 20 or 45 mM mannitol. Fibronectin gene expression was investigated by Northern blot analysis. By day 6, fibronectin mRNA levels increased compared to 5 mM glucose controls with increasing glucose concentration (25 mM, 193%, 50 mM, 314%); high osmolarity due to mannitol did not increase mRNA levels (20 mM and 45 mM mannitol yielded 75 and 104%, respectively). Thus, hypertonic glucose augments fibronectin gene expression in peritoneal mesothelial cells due to the higher concentrations of glucose and not to hyperosmolarity. The glucose-driven increase in fibronectin expression may contribute to the peritoneal fibrosis in CAPD patients.

Animals↗
PubMed1995

Kawasaki disease in Sweden: incidence and clinical features.

The incidence and clinical pattern of patients with Kawasaki disease in Sweden and the outcome of treatment with i.v. immunoglobulin (Sandoglobulin) and aspirin were examined in a national prospective study over a 2-year period. Cases not referred to the study were identified by inquiry. Ninety-nine children were diagnosed as having Kawasaki disease. The annual incidence rate was calculated to be 2.9 per 100,000 in children younger than 16 years of age and 6.2 per 100,000 in children younger than 5 years of age. The median age of our patients was 2.2 years and the male-to-female ratio was 2.3:1. Cardiac ultrasonography revealed abnormalities in 33% of all patients, and 14% of cases in the prospective study had pronounced abnormalities. In most cases (91%) treatment had a prompt effect on fever and morbidity in general, and side effects were mild. Two infants, identified from the inquiry, died from rupture of an aneurysm in the coronary artery in the acute phase of the disease. The risk of cardiac involvement is obvious and emphasizes the importance of early diagnosis and treatment.

Adolescent↗
PubMed1994

Sequence statistics reliably predict stabilizing mutations in a protein domain.

Immunoglobulin variable domains are generally thought of as well conserved platforms providing the base for antigen binding loops of highly varying sequence and structure. However, domain evolution must ensure a balance between optimizing antigen affinity and the requirements of a stable, cooperatively folding domain. Since random mutations can carry a significant penalty for domain stability, constraints are imposed both on the repertoire of germline sequences and on somatic amino acid replacements during affinity maturation. Analyzing these constraints in the conceptual framework of statistical mechanics, we have been able to predict stabilizing mutations in the McPC603 V kappa domain from sequence information alone with better than 60% success rate. The validity of this concept not only has far reaching implications for antibody engineering but may also be generalized to engineer other proteins for higher stability.

Amino Acid Sequence↗
PubMed1993

Serum concentrations of procollagen I C-terminal propeptide, osteocalcin and insulin-like growth factor-I in patients with non-lethal osteogenesis imperfecta.

Serum concentrations of procollagen I C-terminal propeptide (PICP) were studied in 74 patients with various forms of non-lethal osteogenesis imperfecta and 27 unaffected family members. Using the standard deviation (SD) score, PICP concentrations were found to be > or = -1 SD in 16%, between -1 and -2 SD in 26% and < or = -2 SD in 58% of the patients with osteogenesis imperfecta compared to healthy controls. PICP values were lowest in osteogenesis imperfecta type I (-2.4 +/- 0.4 SD, n = 37) followed by type III (-1.9 +/- 0.5 SD, n = 13) and type IV (-1.3 +/- 0.7 SD, n = 20). Four patients with osteogenesis imperfecta with an atypical clinical course had normal or even elevated levels which may indicate heterogeneity in the underlying primary defects. In osteogenesis imperfecta type I, PICP concentrations proved to be a helpful serum marker for pedigree screening. Osteocalcin was high in 25 of 28 patients with osteogenesis imperfecta in the first decade but only in 1 of 18 older patients. Insulin-like growth factor-I was within the normal range in 53 cases of osteogenesis imperfecta, decreased in 2 and elevated in 3 patients. We conclude that PICP concentration is a useful parameter in the clinical management of osteogenesis imperfecta, including the assessment of future therapeutic interventions.

Adolescent↗
PubMed1993

[Osteogenesis imperfecta in childhood and adolescence].

BACKGROUND: 209 patients with osteogenesis imperfecta type I, III and IV were studied to provide data on the natural course of the disease until the end of the second decade. RESULTS: Weight and length at birth were normal in most cases of type I and IV, markedly reduced in type III. Fractures and deformities at birth were most frequent in type III. High fracture rates occurred in type III and IV up to 8-10 years of age. Skeletal deformities developed primarily in the lower extremities and the spine, again most frequently in type III. Radiological features were--besides osteopenia--Wormian bones of the skull, pseudoarthroses, deformity of the pelvis, popcorn epiphyses (most frequent in type III) and hyperplastic callus (most frequent in type IV). Longitudinal growth of patients with type I was in the lower normal range, while patients with type III and IV developed marked growth deficiency. Motor performance was not severely impaired in most cases of type I; however, all type III patients and 71% of type IV patients were confined to a wheelchair in later life. CONCLUSION: As defined, type I patients had a mild clinical course until early adulthood. Type III and IV represented a spectrum of severely affected patients. Although type IV patients were less affected at birth, their postnatal course in some respects resembled that of type III.

Activities of Daily Living↗
PubMed1993

[Properties of an acellular preparation of Bordetella pertussis and its analysis after centrifugation in saccharose gradient].

Acellular preparations were studied which were obtained by a method of acidic extraction from culture of strain Tohama of Bordetella pertussis. Obtained preparations EM I and EM II were exhibiting property of leukocytosis stimulation and were respectively of following values: 43.5 and 19 u LPF/mg of protein. They also caused hemagglutination (150 and 19 u HA/mg of protein). Both preparations were exhibiting protective effect in intracerebral test performed on mice. After differentiation of EM I preparation by preparative centrifugation in saccharose gradient two fractions were obtained, of which lighter was exhibiting high hemagglutinating activity and leukocytosis stimulation (198 u LPF/mg of protein). Heaver fraction contained mainly endotoxin. Applied method permitted for partial purification of acellular preparation of B. pertussis; mainly decrease in its content of endotoxin responsible for high reactogenicity of pertussis vaccines.

Animals↗
PubMed1991

Monocyte phenotype and interleukin-1 production in patients undergoing haemodialysis.

The expression of MHC class II (HLA-DR) and complement receptor (CR1) surface molecules on CD 14+ monocytes were compared with the production of the monokine interleukin-1 beta (IL-1 beta) in patients with endstage renal disease undergoing maintenance haemodialysis (HD) with hollow fibre dialyzers containing cellulose (CE, n = 8) and polysulfone (PS, n = 7) membranes. Monocyte staining was performed in blood samples obtained at the beginning and after 3 h of HD. Analysis of surface marker expression was done by immunofluorescence staining and flow cytometry analysis. Specific fluorescence intensity for both CR1 and class II (HLA-DR) antigens was increased in patients treated with CE membranes at the beginning of a dialysis treatment when compared to healthy control values. Interestingly, after 3 h on dialysis a further increase was noted for CR1 complement receptor expression whereas the increased HLA-DR expression was no longer detectable. In contrast, specific fluorescence intensity for both antigens was not significantly different from controls, either before or after dialysis, in patients treated with PS. The capacity of peripheral blood mononuclear cells to produce IL-1 beta spontaneously in vitro in the two patient groups was found to parallel results on phenotypic expression of surface molecules. The present study demonstrates that functional signs of monocyte activation, as evidenced by an augmented IL-1 beta production, in some patients on long-term HD correlate with an increased expression of two functionally important monocyte surface marker molecules.

Adult↗