The interaction of the polymorphisms in transporter of antigen peptides (TAP) and lymphotoxin alpha (LT-alpha) genes and atopic diseases in the Czech population.

BACKGROUND: Transporter antigen peptide gene (TAP) products are involved in antigen processing. These genes, inducible by interferon gamma, as well as lymphotoxin alpha (LT-alpha), are located in the HLA region. Their involvement in immune response regulation makes them candidate atopy susceptibility genes. OBJECTIVE: This study investigates a possible association between previously identified polymorphisms within the TAP-1 and LT-alpha genes and clinically manifested atopic diseases in the Czech population. METHODS: Caucasian subjects of Czech nationality (n = 427) were included in our study. We examined 184 healthy controls and 243 patients with histories of atopic asthma, allergic rhinitis and atopic dermatitis or their combinations. We used the amplification refractory mutation system polymerase chain reaction to determine TAP-1 gene polymorphisms. LT-alpha genotypes were determined by PCR and restriction analysis by NcoI. RESULTS: No significant differences were found in allele or genotype frequencies of the LT-alpha gene, as well as in polymorphisms for Val-->Ile at codon 333 and Gly-->Asp at codon 637 in the TAP-1 gene between controls and patients. However, analysis of the concurrence of the double genotypes of the TAP-1 polymorphism at codon 333 and the LT-alpha genes showed differences between controls and atopic patients (P < 0.02). CONCLUSION: Several reports have indicated that different HLA products and genes may be risk factors for or protective factors against the development of atopy. We report no association between polymorphisms in the LT-alpha and TAP-1 genes alone and atopic diseases in the central Europe Caucasian (Czech) population, but there was an interesting interaction between the TAP333 and LT-alpha polymorphisms.

Karyotypic and clinical progression of ANLL in a patient with constitutional der(15;21)(q10;q10).

A patient with a constitutional chromosomal abnormality who developed acute nonlymphocytic leukemia (ANLL-M4) at the age of 31 is presented. At the time of diagnosis the only acquired chromosomal change was the presence of a small marker chromosome. The patient was studied periodically for 11 years during his illness with no evidence of karyotypic progression, until the last study, when a deletion of the long arm of chromosome 7 was detected.

[2 cases of Robinow's syndrome with mental retardation]. / Dva prípady Robinowovho syndrómu s mentálnou retardáciou.

The author describes two children, cousins, who have all signs typical for Robinow's syndrome; they are mentally retarded and of gipsy origin. The author assumes autosomal recessive heredity, suggested by the marked skeletal anomaly and consanguinity in the family.

Chronic lymphoproliferative disease of large granular lymphocytes.

An 80-year-old patient has been followed for hepato- and splenomegaly, hemolytic anemia, neutropenia with lymphocytosis with large granular lymphocyte predominance in his peripheral blood, with infiltration of bone marrow, liver and probably also spleen. Determination of surface markers of proliferating lymphocytes in peripheral blood showed a mixed phenotype of T suppressor/cytotoxic and natural killer cells (SIg-, E+, T3+, T8+, EAC+, Leu7-, N901+, NK9+, VIB C5 and VIB E3-, Ia-). An in vitro cytotoxic test showed the functional inactivity of the cells tested also after human leukocyte interferon stimulation. Chromosomal analysis neither of peripheral blood lymphocytes nor of bone marrow cells proved the monoclonality marker. Following long-term prednisone therapy, the improvement of anemia, later also neutropenia accompanied by the decrease of lymphocytes has been achieved. As the disease present in our patient was distinguished only in recent years and in our country has not been reported yet, the details on its clinical, morphologic, hematologic, cytogenetic and mainly immunophenotypic characteristics are given in this paper. The problems concerning classification of the disease and determination of its biological nature are discussed.

Bovine superoxide dismutase in Fanconi anaemia. Therapeutic trial in two patients.

Bovine superoxide dismutase (SOD) (Peroxinorm, Grünenthal Stolberg) was injected intramuscularly or subcutaneously in a daily dose of 4 mg over a period of six weeks into two patients with Fanconi anaemia. The effects (measured by the decrease of chromosome aberrations in blood lymphocytes and the increase in blood cells in venous blood) were evident but temporary. The hypothetical mode of action of SOD and the failure of a prolonged therapeutic effect are discussed.

Homozygosity for fragile site at 17p12 in a 28-year-old healthy man.

In a family two heterozygous children and a homozygous phenotypically normal father with a fragile site at 17p12 were discovered. This observation confirms the opinion that even homozygosity for this fragile site is phenotypically harmless.

Clonal evolution of karyotype in blastic phase of CML.

A patient with chronic myelocytic leukemia (CML) had a Philadelphia chromosome--Ph1(t(9q +; 22q--)) in all evaluated bone marrow cells at the time of diagnosis. After 29 months of intermittent therapy (chemotherapy and immunotherapy) and 2 months before clinical signs of blastic phase developed, three additional cell lines in bone marrow and peripheral blood appeared: one line with extra chromosome Ph1, another one in which chromosome Y disappeared, and the third line with extra chromosome No. 13, evidently derived from the X-monosomie cell line. Five weeks before death a variable hypodiploidy was found in more than 50% mitoses. The patient died 47 months after the establishment of CML and seven months after the onset of the blastic phase.

[Diagnostic value of particular symptoms in monosomy X. Evaluated on the basis of experiences with 34 own cases (author's transl)]. / Diagnostischer Aussagewert von Untersuchungsbefunden bei der Monosomie X. Ermittelt an 34 eigenen Fällen.

Ten cases of monosomy X and caryotype 45,X, and 24 cases of the disorder with various forms of mosaicism are reported. The diagnostic significance of particular stigmata is underlined, and the possibility stressed to demonstrate a hidden pterygium colli by declining the patient's head laterally. Moreover, several peculiarities of individual cases are shown: In three girls with mosaicism, spontaneous puberty was observed, however, in two of them, it was followed by precocious menopause at the age of 14 and 18 years, respectively. The necessity of caryotyping in growth-retarded girls with secondary amenorrhoea or with a ren arcuatus or unilateral solitary kidney is emphasized. High values of urinary gonadotropins in girls without signs of puberty or with precocious menopause, indicate the need for substitution. This therapy leads to the appearence of secondary sex phenomena and menstruation, and at the same time prevents osteoporotic changes.