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Biomedical subjects

B Belohradsky

Publications and source records attributed to B Belohradsky.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent pericarditis in children: elevated cardiac autoantibodies.

UNLABELLED: Recurrent pericarditis is a rare disease in childhood. Nevertheless, it may represent a challenge to the clinician due to its resistance to anti-inflammatory treatment. The initial etiology often remains unclear; specific laboratory parameters predicting the frequency or severity of the recurrences are lacking. We report on four patients with recurrent pericarditis in whom antimyolemmal antibodies (AMLAs) were detected. A prolonged persistence of IgM-type AMLAs was found in three patients: two of them presented with acute inflammation as the initial event and one with 48 recurrences during 5.5 years. The fourth patient showed a fast conversion from IgM to IgG-type AMLAs after a less acute initial presentation and showed 4 mild recurrences during the 48-month follow-up. CONCLUSION: We were able to detect AMLAs in four children with recurrent pericarditis. This finding may be attributed to an auto-immunological disease following a first, acute event. We propose the detection of AMLAs in all children with unexplained recurrent pericarditis. Pediatric patients with a persistence of IgM-type AMLAs may face frequent recurrences and should be monitored therefore more closely. In addition, medical treatment may be changed in these patients with a slower tapering of the dosage of steroidal and non-steroidal antiinflammatory drugs.

Acute Disease↗
PubMed2002

Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody.

The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence.

Adolescent↗
PubMed1997

Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.

We present clinical data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22q11. Twenty-eight percent of the cases where parents had been tested had inherited deletions, with a marked excess of maternally inherited deletions (maternal 61, paternal 18). Eight percent of the patients had died, over half of these within a month of birth and the majority within 6 months. All but one of the deaths were the result of congenital heart disease. Clinically significant immunological problems were very uncommon. Nine percent of patients had cleft palate and 32% had velopharyngeal insufficiency, 60% of patients were hypocalcaemic, 75% of patients had cardiac problems, and 36% of patients who had abdominal ultrasound had a renal abnormality. Sixty-two percent of surviving patients were developmentally normal or had only mild learning problems. The majority of patients were constitutionally small, with 36% of patients below the 3rd centile for either height or weight parameters.

Adolescent↗
PubMed1995

A primary T-cell immunodeficiency associated with defective transmembrane calcium influx.

We investigated a T-cell activation deficiency in a 3-month-old boy with protracted diarrhea, serious cytomegalovirus pneumonia, and a family history (in a brother) of cytomegalovirus infection and toxoplasmosis. In spite of detection of normal number of peripheral lymphocytes, T cells did not proliferate after activation by anti-CD3 and anti-CD2 antibodies, although proliferation induced by antigens was detectable. We sought to determine the origin of this defect as it potentially represented a valuable tool to analyze T-cell physiology. T-cell activation by anti-CD3 antibody or phytohemagglutinin (PHA) led to reduced interleukin-2 (IL-2) production and abnormal nuclear factor-activated T cell (NF-AT; a complex regulating the IL-2 gene transcription) binding activity to a specific oligonucleotide. T-cell proliferation was restored by IL-2. Early events of T-cell activation, such as anti-CD3 antibody-induced cellular protein tyrosine phosphorylation, p59fyn and p56lck kinase activities, and phosphoinositide turnover, were found to be normal. In contrast, anti-CD3 antibody-induced Ca2+ flux was grossly abnormal. Release from endoplasmic reticulum stores was detectable as tested in the presence of anti-CD3 antibody or thapsigargin after cell membrane depolarization in a K+ rich medium, whereas extracellular entry of Ca2+ was defective. The latter abnormality was not secondary to defective K+ channel function, which was found to be normal. A similar defect was found in other hematopoietic cell lineages and in fibroblasts as evaluated by both cytometry and digital video imaging experiments at a single-cell level. This primary T-cell immunodeficiency appears, thus, to be due to defective Ca2+ entry through the plasma membrane. The same abnormality did not alter B-cell proliferation, platelet function, and polymorphonuclear neutrophil (PMN) function. Elucidation of the mechanism underlying this defect would help to understand the physiology of Ca2+ mobilization in T cells.

Antigens, CD↗
PubMed1995

DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor.

ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by instability of the pericentromeric heterochromatin predominantly of chromosomes 1 and 16. DNA methylation studies in two unrelated ICFS patients provide further evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific disturbances of chromatin structure take place within the satellite 2 DNA regions, as demonstrated by fluorescence in situ hybridization analysis. Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19 have revealed hypomethylation to different degrees in both patients; this provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell fusion experiments have revealed a distinct reduction of chromosomal abnormalities in ICFS cells after fusion with normal cells, suggesting that the abnormalities are caused by the loss of function of an as yet unknown trans acting factor. Although it is now clear that wide-spread DNA hypomethylation is a characteristic feature of ICFS, neither the cause and mechanism of hypomethylation nor their relationship to the clinical symptoms is known. We speculate that a phenotypic effect might result from tissue-dependent abnormal gene expression and/or from a possible structural disturbance of DNA domains, which, with respect to the immunodeficiency, partially prevents the normal somatic recombinations in immunologically active cells.

Cell Line, Transformed↗
PubMed1995

DiGeorge syndrome and partial monosomy 10p: case report and review.

DiGeorge syndrome (DGS) is predominantly caused by partial monosomy 22q11, but a subset of patients with DGS show deletions of 10p or other chromosomal abnormalities. The authors describe a 20 months old girl with DGS and a monosomy 10p bringing the number of DGS patients with this chromosomal abnormality to nine. She has a monosomy 10p13-pter and a trisomy 10q26-qter due to a meiotic recombination of a maternal inversion (10) (p13q26). The proposita's phenotype demonstrates typical features of the del (10p) syndrome which include mental retardation, abnormally shaped skull, hypertelorism, low nasal bridge, micrognathia, dysmorphic low set ears, short neck, foot abnormalities, and cardiac defect. The diagnosis of DGS was made unequivocally within the first weeks of life because of the typical features-cardiac defect, hypoplastic thymus, T-cell defect, hypocalcemia, and hypoparathyroidism. The common DGS mutation-microdeletion 22q11-was excluded by FISH analysis, and the breakpoints on chromosome 10 were mapped between D10S189 and D10S191 on the short arm and proximal to D10S25 on the long arm.

Chromosome Deletion↗
PubMed1994

[Bilateral ureteral obstruction by granuloma formation in chronic granulomatosis].

A 24-year-old patient with chronic granulomatous disease had bilateral hydronephrosis resulting from ureteral granuloma formation. He was treated with high-dose steroids, antibiotics and percutaneous nephrostomy. The etiology, incidence, clinical findings and treatment of chronic granulomatous disease are discussed.

Adrenal Cortex Hormones↗
PubMed1993

Pyrrolidine dithiocarbamate inhibits NF-kappa B mobilization and TNF production in human monocytes.

The human TNF promoter contains four potential nuclear factor-kappa B (NF-kappa B)-binding sites, with the strongest binding seen for the -605 motif. Nuclear extracts from unstimulated cells of the human monocytic cell line, Mono Mac 6, contain one specific binding protein (complex II), consistent with a constitutive p50 homodimer. Stimulation of Mono Mac 6 cells with LPS will increase complex II and will strongly induce a second specific complex (complex I), which represents the p50/65 heterodimer. Treatment of Mono Mac 6 cells with pyrrolidine-dithiocarbamate (PDTC) at 300 microM will block the LPS-induced complex I almost completely and will reduce complex II to the constitutive level. Binding activity of other nuclear factors that recognize the SP-1 and c/EBP motifs of the human TNF promoter is not affected by such treatment. Northern blot analysis demonstrates that PDTC treatment will strongly reduce LPS-induced TNF transcripts. Secreted TNF protein as detected in the Wehi 164S/ActD bioassay and in a sandwich immunoassay was similarly reduced by PDTC. Kinetic analyses show that after LPS stimulation, NF-kappa B will peak at 1 h, TNF transcript prevalence at 2 h, and TNF protein at 4 h. PDTC did not shift this response to LPS to a later time, but suppressed NF-kappa B mobilization, TNF transcripts, and TNF protein over the entire 8-h observation period. Analysis of freshly isolated, LPS-stimulated blood monocytes showed a similar blockade of NF-kappa B. Furthermore, in these primary cells, induction of TNF transcripts, as determined by Northern blot analysis and by quantitative polymerase chain reaction, was prevented by PDTC as was TNF protein production. These data show that dithiocarbamates can profoundly affect cytokine expression and suggest that NF-kappa B is involved in LPS-induced TNF gene expression in human monocytes.

Binding Sites↗
PubMed1992

Partial trisomy 8q. Two case reports with maternal translocation and inverted insertion: phenotype analyses and reflections on the risk.

Partial trisomy 8qter-->q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here. Patient 1 inherited the derivative (2) of a balanced maternal reciprocal translocation t(2;8)(qter;q2300) after 2:2 disjunction and adjacent-1 segregation, and is trisomic for the segment 8qter-->q2300. Patient 2 inherited a recombinant (8) of a balanced maternal inverted insertion inv ins(8)(q1300;q2300q24.2) and is trisomic for the segment 8q24.2-->q2300. The phenotype of both patients is described and compared to the spectrum of symptoms established from the 15 literature cases. This spectrum contains all features observed with a frequency of > = 50%. Patient 1 had 35% of the features of this spectrum; Patient 2 had 47%. The intrauterine survival probability of unbalanced offspring is assumed to be the same in both cases, as nearly the same segments are trisomic. The pedigrees indicate that the inversion carrier may have a reduced production probability of unbalanced gametes and therefore a reduced risk compared to the translocation carrier.

Abnormalities, Multiple↗
PubMed1988

[Diagnosis and therapy of pyonephrosis in infancy and childhood].

A diagnostic schedule in pyonephrosis was followed in thirteen infants and children. Obstruction of the urinary tract could be demonstrated in 12 patients, non-obstructive pyonephrosis was present in one case. Congenital obstructive malformation of the urinary tract was found in 7 patients, obstruction was acquired in 5. Sonographically, pyonephrosis could be diagnosed in 8 patients (64.3%). Excretory urography (10/13) was helpful in no actual case. Sonographical-guided percutaneous nephrostomies were performed in 5 patients and operative nephrostomies in 4. Emergency-nephrectomies were done in 4 patients. A tap of the renal pelvis is the best way for early diagnosis whenever pyonephrosis is clinically suspected.

Adolescent↗
PubMed1985

Severe combined immunodeficiency: treatment by bone marrow transplantation in 15 infants using HLA-haploidentical donors.

In 15 infants with severe combined immunodeficiency (SCID), immunological reconstitution was attempted by bone marrow transplantation (BMT) from HLA-haplo-identical parents. To prevent graft versus host disease (GvHD), marrow grafts were depleted of contaminating T-lymphocytes using lectin agglutination and rosette formation with sheep red blood cells. Thirteen patients received transplants without undergoing prior cytoreductive conditioning. Eleven of these developed donor-dependent T-cell functions, two failed to do this. One of these two as well as two further patients received cytoreductive treatment prior to repeat and to first transplants and in two, complete lymphohemopoietic reconstitution was observed. Of the 15 patients who received transplants, 11 are currently alive. Two recently treated patients remain in the hospital, nine are at home with stable T-cell functions. Normal humoral immune functions have developed upto now in three patients. In the others, gamma globulins are regularly substituted. Complications of acute or chronic GvHD were not observed with the exception of one case who developed transient GvHD of the skin. These results suggest that in a majority of patients with SCID, T-cell functions can develop without GvHD following haploidentical, T-cell-depleted BMT. Exceptional patients require preconditioning to allow donor cell engraftment, an approach that also appears to facilitate reconstitution of humoral immune functions.

Bone Marrow Transplantation↗
PubMed1985

Active immunization against varicella of children with acute leukaemia or other malignancies on maintenance chemotherapy.

Twenty-six patients with acute leukaemia and other malignancies susceptible to varicella were vaccinated with the Oka-strain live attenuated varicella vaccine during maintenance chemotherapy. All recipients showed no adverse clinical reactions. There was no spread of vaccine virus. Seroconversion was 94% in seronegative patients. Among those having low antibody titres before vaccination, a booster effect was demonstrable in 56%. None of the seroconverted recipients contracted varicella despite documented contact exposure. No case of herpes zoster occurred. The results suggest that, in immunocompromised children, live varicella vaccination has a protective effect against varicella infection which may result in a mortality rate of up to 7% in these patients.

Acute Disease↗
PubMed1981

[Bone marrow transplantation for aplastic anaemia (author's transl)].

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

Adolescent↗
PubMed1981

[Altered bacterial periurethral flora in young girls with chronic, recurrent urinary tract infections? (author's transl)].

Assuming a local weakness in the defence system to be responsible for chronic, recurrent infection of the urinary tract in young girls, we made 86 determinations of the bacterial periurethral flora from 70 female patients aged between five and eleven years. Within three patient groups (urologically healthy, temporarily free from infection, currently suffering an acute attack of chronic, recurrent urinary tract infection), we found gram-negative bacteria in 1/20 of the healthy children, in 1/2 of those temporarily free from infection and in all children suffering an acute attack. Enterococci (the accompanying flora) was found in 1/20, 1/2 of the children respectively. In both cases, the differences were significant (chi 2-Test, p less than 0.01). In comparison to healthy children, the more children, in 1/2 of those temporarily free from infection and in all children suffering an acute attack. Enterococci (the accompanying flora) was found in 1/20, 1/2 of the children respectively. In both cases, the differences were significant (chi 2-Test, p less than 0.01). In comparison to healthy children, the more children, in 1/2 of those temporarily free from infection and in all children suffering an acute attack. Enterococci (the accompanying flora) was found in 1/20, 1/2 of the children respectively. In both cases, the differences were significant (chi 2-Test, p less than 0.01). In comparison to healthy children, the more frequent colonization of children who were not currently infected, but who were prone to infection, was seen particularly as an indication of an intermittent local weakness in the defence system, possibly occurring when a defence mechanism occasionally falls short of a threshold level, thus allowing an infection to set in.

Child↗