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Biomedical subjects

A I Berkel

Publications and source records attributed to A I Berkel.

At least 19 recordsLinked to original sources
PubMed2000

Isolated cutaneous response to granulocyte-monocyte colony stimulating factor in fatal idiopathic disseminated Bacillus-Calmette-Guerin infection.

UNLABELLED: Severe disseminated Bacillus-Calmette-Guerin (BCG) infection is very rare and has been regarded as idiopathic when no immunodeficiency is present. This entity seems to be due to several new types of inherited abnormalities in the pathways important in defence against Mycobacteria. Although improvement with interferon-gamma (IFN-gamma) has been reported in some patients, to our knowledge there are no reports on the effect of other cytokines in the treatment of these patients. We report here the clinical response to IFN-gamma and granulocyte-monocyte colony stimulating factor (GM-CSF) treatment in a patient with idiopathic disseminated BCG infection who failed to respond to multiple antimycobacterial agents. The patient showed partial and transitory response to IFN-gamma, however, GM-CSF treatment led to rapid improvement of skin lesions within 2 weeks without any effect on the progression of the disease in the other organ systems. CONCLUSION: The response of idiopathic disseminated Bacillus-Calmette-Guerin infection to granulocyte-monocyte colony stimulating factor treatment was limited to cutaneous lesions. Granulocyte-monocyte colony stimulating factor may have acted to promote wound healing or the levels of this factor achieved in other affected organs may have been inadequate.

BCG Vaccine↗
PubMed2000

Molecular, genetic and epidemiologic studies on selective complete C1q deficiency in Turkey.

Selective complete C1q deficiencies (SCDC1q) of the complement component C1q are rare genetic disorders with high prevalence of lupus-erythematosus-like symptoms and recurrent infections. Among the 41 published cases from 23 families, 10 derive from 6 Turkish families. One particular mutation leading to a stop codon in the C1q A gene was first identified in members of a Gypsy family from the Slovac Republic. Later the same mutation has been found in all cases in four SCDC1q families from Turkey suggesting that one particular defective allele may be present in the populations of Southeastern Europe and Turkey. This study was undertaken to investigate the frequency of C-->T mutation in exon II of C1qA gene in Turkish population by using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Among the 1544 patients from 15 pediatric departments and an additional 89 SLE patients of various ages no C1qA gene mutation was found. There were 43 heterozygous and 4 homozygous mutations in 161 family members or relatives investigated from the 4 families known with SCDC1q. Among the 223 inhabitants who were nonrelative to the 3 SCDC1q families living in the same village were screened for mutation and one heterozygous individual was observed. Although this mutant allele appears to be at a low prevalence in the population tested, individuals with recurrent infections or symptoms of lupus erythematosus-like syndrome should be tested for this mutation to rule out this type of C1q deficiency.

Autoimmune Diseases↗
PubMed2000

Polymorphism of the fourth component of complement in Turks.

An analysis of polymorphism in the fourth component of human complement (C4) was performed on EDTA-plasma from 142 unrelated, randomly selected Turks without collagen-vascular disease or recurrent infections. Plasma samples treated with neuraminidase and carboxypeptidase-B were subjected to high-voltage agarose gel electrophoresis followed by immunofixation. C4B allotypes were further detected in some samples by Western blots with monoclonal antibody 1228 (anti-C4B/Ch1 reactivity). The frequencies of C4A and C4B alleles were determined. Allele C4B*5, which has been found to be relatively common in Asian (Oriental) populations, was not detected in this study. No specific predilection could be noted among the rare variants. C4A*3-C4B*1 was the most common haplotype (n = 40/142, or 28%) but was found less frequently than in Caucasian populations. This finding may be the result of the limited number of samples examined. C4A and/or C4B null allotypes were seen in 49 of 142 (34.6%) subjects. The most frequent C4 null allotype seen was C4B null (37/142, or 26%): 28 subjects had one C4B null allele; 1 had a homozygous deficiency of C4B (C4B*QO, *QO) and 7 had C4A*QO C4B*QO, a double heterozygous haplotype. Frequencies of homozygous haplotype C4A*Q0-C4B*Q0 in the population studied were found to be 0.007. The results of this study demonstrate that the genetic composition of the Turkish population exhibits both similarities and differences with the European population, and ranges between Caucasian and Mongoloid (Asian) populations.

Alleles↗
PubMed1999

Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia.

Various factors seem to be etiologic in the susceptibility to sinopulmonary infections in ataxia-telangiectasia (A-T) patients, i.e., low serum and salivary IgA, low serum IgG2, and even aspiration of saliva. S. pneumoniae is a common pathogen responsible from pulmonary infections and impaired antibody response to polysaccharide antigens is seen in patients with IgG2 and IgA deficiency as well as patients with CVID and WAS. We studied IgG-type antibody production to six pneumococcal serotypes in 29 A-T patients by ELISA before and 3-4 weeks after pneumococcal vaccine. The response was considered positive when the antibody titer was >10 U/ml but weak when the titer was 10-20 U/ml. Twenty-two of 29 (76%) patients did not respond to any of the serotypes, 5 (17%) showed a positive response to one serotype, 1 (3.4%) to two serotypes, and 1 (3.4%) to four serotypes. With conversion to gravimetric units (ng IgG/ml) and >1800 ng/ml (300 ng Ab N/ml) considered a positive response, 5 of 29 (17.2%) patients showed a positive response (300 ng ab N/ml) to two or fewer serotypes. All patients tested produced IgG antibody to tetanus toxoid. Sixteen of 27 (59.3%) patients had low IgG2 and four (14.8%) had low IgG3 levels, while 18 (62.1%) of 29 patients had low serum IgA. No correlation was found either between serum Ig isotype levels and antipolysaccharide antibody response or between susceptibility to infection and antibody production. The mechanism responsible for disturbed antipolysaccharide (TI-2 antigen) antibody production in patients with A-T needs to be investigated. It may provide additional information on the function of the ATM gene product and be helpful in clarifying the role of B cells and contribution of T cells in TI-2 responses.

Adolescent↗
PubMed1997

Development of systemic lupus erythematosus in a patient with selective complete C1q deficiency.

UNLABELLED: A 7-year-old male with recurrent erythematous and desquamated skin lesions and respiratory infections was diagnosed as selective complete C1q deficiency following detailed studies of the complement system. His asymptomatic sister also had selective complete C1q deficiency. During a follow up period of 3 years, his skin lesions persisted, he suffered from recurrent bronchopneumonias and glomerulonephritis developed. Renal function deteriorated with the appearance of anti-DNA antibodies. Renal biopsy was consistent with systemic lupus erythematosus. The patient was treated with immunosuppressive drugs, but died of renal failure. It is postulated that in this patient defective clearance of antigen-antibody complexes by the reticulo-endothelial system resulted in progressive renal disease as observed in other complement deficiencies. A retrospective molecular study disclosed a point mutation in the ClqA chain gene in a heterozygous state in parents and two siblings; in a homozygous state in the asymptomatic sister. The reason why some individuals with this defect are asymptomatic is not known at present. Diagnosis of heterozygotes by molecular studies is extremely important to give genetic counselling to the family. CONCLUSION: Patients with recurrent infections, erythematous desquamative skin lesions, malar rash and oral mucosal involvement should be screened for complement C1q deficiency.

Blood Protein Disorders↗
PubMed1997

Multiple identification of a particular type of hereditary C1q deficiency in the Turkish population: review of the cases and additional genetic and functional analysis.

Complete selective deficiencies of the complement component C1q are rare genetic disorders that are associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. All C1q deficiencies studied at the genetic level revealed single-base mutations leading to termination codons, frameshifts or amino acid exchanges and these were thought to be responsible for the defects as no other aberrations were found. One particular mutation, leading to a stop codon in the C1qA gene, was first identified in members of a Gypsy family from the Slovak Republic. The same mutation has been found in all cases of C1q deficiency from Turkey that have been investigated. Here we present the results of genetic analysis of the C1q genes from three families and give information on further C1q-deficient members of two families that have not been reported elsewhere. Reviewing all cases of C1q deficiency from Turkey prompted us to hypothesize that one particular defective allele is present in the population of southeast Europe and Turkey. With a novel polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and allele-specific PCR we are able to detect even asymptomatic, heterozygous carriers of the mutation, which will enable genetic counseling of the affected individuals.

Amino Acid Sequence↗
PubMed1996

Dyskeratosis congenita: unusual onset with isolated neutropenia at an early age.

A 3.5 year old male patient with dyskeratosis congenita (DC) presented at the age of 13 months with isolated neutropenia preceding characteristic skin findings. The average absolute neutrophil count of 500/mm3 persisted without the presence of anemia or thrombocytopenia during the follow up. Neutropenia responded to granulocyte-colony stimulating factor (G-CSF) at a dose of 10 micrograms/kg per day. Immunologic findings were normal as was the chromosomal stability and sister chromatid exchange.

Child, Preschool↗
PubMed1996

Homozygous C2 deficiency: association with defective alternative pathway function and immunoglobulin deficiency.

Deficiency in the second component of complement (C2) is the most common homozygous complement deficiency. While approximately half of the affected individuals are apparently healthy, C2 deficiency may be associated with autoimmune diseases and rarely increased susceptibility to infection. We report 5 patients who had homozygous type I C2 deficiency in two families. Three of them suffered from frequent infections. These symptomatic patients had additional risk factors; the index cases in the first and the second family had IgG2 deficiency and IgA deficiency, respectively, and alternative complement pathway hemolytic activity was also low in both of them and in the sibling of the first index case. These results emphasize the probable role of other immunologic defects in the clinical presentation of C2 deficiency.

Child↗
PubMed1995

Selective IgA deficiency with unusual features: development of common variable immunodeficiency, Sjögren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura.

We report on a girl with selective IgA deficiency and persistently low complement component 4 (C4) levels compatible with heterozygous C4 deficiency. Deterioration of her serum immunoglobulin levels and transition to common variable immunodeficiency were observed within a 5 year follow-up. She also developed Sjögren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura. While these abnormalities have been described before in various combinations, to our knowledge, they have not been reported in a single individual.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

Ataxia-telangiectasia: a variant with altered in vitro phenotype of fibroblast cells.

The clinical and cellular phenotype of ataxia telangiectasia (AT) has been extensively documented in numerous patients of different ethnic groups and is characterized by several specific laboratory hallmarks, such as chromosomal instability, profound radiosensitivity and radioresistant DNA synthesis. Several recent reports have, however, shown variations on this theme. This article describes 2 Turkish siblings with AT, who showed a typical but somewhat more prolonged clinical course of the disease and altered characteristics of fibroblast cells, compared to the 'classical' AT cellular phenotype. Fibroblast strains derived from these patients showed a normal cellular life span, moderate degrees of chromosomal instability and sensitivity to the lethal effects of X-rays and neocarzinostatin, and lack of radioresistant DNA synthesis. A compilation of the literature on 'AT variants' and 'AT-like' syndromes shows that in addition to the internal variability of AT, this disease occupies a limited segment within a large spectrum of clinical and cellular features, which are common to a variety of syndromes. Each of these syndromes covers a different segment in this spectrum. The genetic basis of this family of disorders might be complex.

Ataxia Telangiectasia↗
PubMed1986

Lymphocyte gamma-glutamyltranspeptidase activity in ataxia-telangiectasia.

gamma-Glutamyltranspeptidase (GGTP) is a membrane-bound enzyme, that catalyzes gamma-glutamyl transfer from gamma-glutamyl compounds to amino acid and peptide acceptors. One of the most important clinical findings about ataxia-telangiectasia (A-T), a multisystemic and autosomal-recessive disease, is dysfunction of the immune system. In this study, the activity of GGTP was determined in the lymphocytes from patients with A-T. Lymphocyte GGTP activity in A-T patients was found to be significantly lower than that of control lymphocytes (P less than 0.001). This change may be due to the abnormality in the membrane of lymphocytes of A-T patients.

Adolescent↗
PubMed1985

Studies on lymphocyte cell surface in ataxia-telangiectasia.

Lymphocyte surface proteins of patients with ataxia-telangiectasia were separated by polyacrylamide gel electrophoresis and compared by autoradiography. The patients lacked one of the two main bands (Band I at the origin). The second main band (Band II) was absent in some cases. All patients had one or two additional bands of smaller molecular weight than Band II except one case who had no band detectable. In the patients, alkaline phosphatase, total ATPase and Mg2+. ATPase were increased but 5'-nucleotidase was normal. The results suggest abnormality in the plasma membranes of the patients' lymphocytes.

5'-Nucleotidase↗
PubMed1985

Immune response to Epstein-Barr virus (EBV) in ataxia-telangiectasia: EBV-specific antibody patterns and their relation to cell-mediated immunity.

Epstein-Barr virus (EBV)-specific antibody titers were investigated in 60 patients with ataxia-telangiectasia (AT) and 22 healthy members of their families. In addition, we studied 36 patients with primary immunodeficiencies, Behçet disease, and other conditions and 61 unrelated healthy controls. Twenty-seven AT patients were examined sequentially at intervals varying from 2 months to 8 years. The AT patients showed an increased incidence (66.6%) of high antibody titers (greater than or equal to 1:320) to viral capsid antigen (VCA) and also a high incidence (35%) of antibody titers to early antigens (EA), but low titers (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 35% of the patients. The geometric mean titers (GMT) of antibodies to VCA were five to six times higher; those of anti-EBNA were five times lower in AT patients as compared with control groups. In serial determinations, anti-VCA and anti-EBNA titers remained constant with the exceptions of two patients who developed ALL and Hodgkin lymphoma. The patients with other diseases did not differ significantly from the controls, with the exception of lower titers (less than 1:10) of anti-EBNA (52.8%). AT patients with low anti-EBNA titers tended to have more advanced T-cell deficiencies than those with moderate anti-EBNA titers, as detected by total lymphocyte and E-rosetting cell counts and skin test responses. The percentage of patients with low serum IgA levels was found to be higher in the low anti-EBNA group than in the moderate anti-EBNA group (44.5 vs 20%).

Adolescent↗
PubMed1985

Spontaneous cytotoxicity against measles virus infected and K562 cells in normal subjects and subacute sclerosing panencephalitis.

Spontaneous cytotoxicity towards LU106 (heteroploid human lung cell line) cells persistently and acutely infected with measles virus was studied in measles immune and nonimmune healthy subjects and SSPE patients. K562 (myeloid cell line) cells were also used to detect the NK activity. Specific cytotoxic responses for measles immune and nonimmune donors were not significantly different for both persistently and acutely measles infected LU106 cells indicating that our assay system detected NK activity. Cytotoxic responses of SSPE patients against virus infected and K562 cells were found to be within normal limits in 3 and 5 patients respectively.

Cell Line↗