[Molecular genetic characterization of chronic lymphocytic leukemia aggressivity in Czech patients: a nucleotide variability of genes coding for heavy chain of immunoglobulin]. / Molekulárne -genetická charakterizace agresivity chronické lymfocytárni leukémie u ceských pacientu: nukleotidová variabilita genu kódujících syntézu tezkého retezce imunoglobulinu.

BACKGROUND: Chronic lymphocytic leukemia is a heterogeneous disease manifesting with a variable clinical course. It is evident from many studies, that the division into two main prognostic categories is possible on the basis of mutation status of the immunoglobulin heavy-chain gene. The objective of our work was to identify a presence or absence of IgVH gene mutations in B-CLL patients which are monitored or treated on hematological clinics and to determine the presence of individual D and J, subgenes in malignant population of B-cells. METHODS AND RESULTS: A nucleotide sequence of IgVH gene of neoplastic cells was analyzed by appropriate molecular-genetic methods. RNA/cDNA was collected from 358 patients and a spectrum of individual subgenes translocations was identified. Our results show that 56.3% of patients manifested an unmutated variable (VH) segment. It is expected from the published data that this group of patients will suffer from aggressive course of the disease and will exhibit a substantially shorter survival in comparison to patients possessing somatic hypermutations. An expanded population of leukemic B-cells showed increased occurrence of clones whose variable segments belong to three different families. VH3 alleles are the ones most frequently used. A frequency of unmutated alleles is prominently shifted into families with V I homology. The preferred "diversity and joining" segments are D3, D2 and JH 4 and JH 6. CONCLUSIONS: The analysis of heavy chain immunoglobulin gene after recombinant VH-D-J11 segments translocation belongs to a standard hematooncological investigation. The results are an important prognostic criterion for prediction of expected disease aggressivity and for a minimal residual disease monitoring.

[Acute interstitial nephritis with uveitis in children and adolescents]. / Akutní intersticiální nefritida s uveitidou u detí a mladistvých.

Acute non-suppurative tubulointerstitial nephritis was recorded within a five-month interval in 1988 in one girl and two boys aged 15, 16 and 12 years. The common feature was non-selective proteinuria, slight glycosuria, anaemia, a sedimentation rate of more than 100 mm/2 hrs hyperatotaemia not calling for dialyzation treatment (268, 354 and 266 mumol/l plasma creatinine resp.), a markedly impaired concentrating capacity (540, 593 and 520 mOsm/kg urine resp.). In all patients circulating serum immunocomplexes were elevated (PEG-IKEM). One patient developed acute uveitis at the onset of the disease, the remainder after 5 and 6 months resp. and in all there was a tendency of a protracted course and relapses resp. In two patients uveitis was diagnosed by an aimed examination by means of a slit lamp at a time when there were not yet any clear signs of affection of the eyes. All patients were subjected to percutaneous renal biopsy which revealed an interstitium with uneven lymphoplasmacytic cellulization with infrequent eosinophil and neutrophil polynuclear cells. Electron microscopy revealed sections of varying size with fibrotization of the tubular basal membrane; the glomerular changes were not typical. All patients had prednisone treatment and their renal functions were gradually restored. Despite extensive serological examinations, the aetiology was not cleared, however before the onset of the disease the patients had penicillin, cotrimoxazol and erythromycin resp.