Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

DNA histogram typing and DNA index measurements in 508 invasive breast carcinomas from fine-needle aspirates and imprint smears as opposed to formalin-fixed paraffin-embedded tissues

Morphometric, i.e. nuclear area (NA), and densitometric, i.e. nuclear DNA content, features were characterized in a series of 508 invasive ductal breast carcinomas. The specimens analyzed were from three distinct sources, i.e. fresh material (252 fine-needle aspirates as opposed to 147 imprint smears) immediately fixed in EFA fixative as opposed to archive material, i.e. 109 formalin-fixed paraffin-embedded tumours that were subsequently deparaffinized. Morphonuclear parameters were computed on Feulgen-stained nuclei by means of a cell image processor. Our results show that the development of nuclear size and DNA content in function of anatomopathological grading is approximately the same for specimens of breast cancer provided by FNAs, imprint smears and formalin-fixed paraffin-embedded tissues. However, in these latter instances it seems that part of the morphometric information is slightly modified in relation to the information obtained from fresh material directly fixed in EFA for cytophotometric analysis. The greatest discriminatory power of the morphometric parameters was obtained in relation to the FNAs. Lastly, in the present study we come out in favor of the idea that henceforth it would be preferable to express results concerning nuclear DNA content as DNA histogram types rather than in terms of DNA indices.     

Interaction of aluminum with biomolecules - any relevance to Alzheimer's disease?

The possible involvement of aluminum in Alzheimer's disease (AD) is discussed focusing, on the one hand, on a critical review of the analytical results concerning the brain aluminum content of AD patients, and on the other hand, on the in vitro interactions of AI(III) with biologically relevant potential AI(III) binders occurring in intracellular and/or extracellular fluids. The biomolecules considered are such as amino acids, organic and inorganic phosphates, nucleotides, catecholamines and transferrin. It is quite clear from the results that definition of the actual AI(III) species present in the biological systems is essentially important in any studies of the neurotoxic role of aluminum.     

Falloposcopy after prostaglandin treatment of tubal pregnancy

We report on a tubal pregnancy treated with prostaglandin F₂ locally. Falloposcopy two years afterwards showed multiple, non obstructive adhesions of the tubal epithelium.     

In-vitro characterization of dihydrotestosterone-induced, epidermal growth factor-induced and basic fibroblastic growth factor-induced modifications in the growth dynamics of the human prostate-cancer cell-line lncap, du145 and pc3

The influence of dihydrotestosterone (DHT), the epithelial growth factor (EGF) and the basic fibroblast growth factor (bFGF) was investigated on LNCaP, DU145 and PC3 cell growth, which represents the ratio between cell gain (cell proliferation) and cell loss (cell death). In the present study, cell growth was assessed by means of the computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques, which enabled the cell colony patterns, i.e. their density and level of organisation, to be determined. The results from a previous study (Janssen et al, Prostate, in press) combined with those of the present one show that DHT was found to activate proliferation of the LNCaP model, as evidenced by increase in size of colonies, increase in number of cells within colonies, increase in cell colony density and, accordingly, decrease in mean segment length value (which is the distance between adjacent cell nuclei). Using the same criteria, DHT was found inhibitory on growth of DU145 cell line, and devoid of significant effect on PC3 cell line. Basic FGF was found to be a powerful stimulator of growth of PC3 cell Line and to induce a weaker stimulation of DU145 cell line. On LNCaP cell line, it increased the size of colonies without increase of the number of cells per colony. This feature can be explained by a decrease in cell colony density. With respect to the same colonies, the proliferation index (percentage of cells in the S+G2 phases of the cell cycle) was found similar to that of the controls. This suggests that the increase in the size of the colonies is due to a difference of spreading of the cells on their supports. EGF had no significant effect on LNCaP and PC3 models, and was decreasing cell density of DU145 colonies.     

Clinical, laboratorial, and therapeutic aspects of 46 children with Henoch-Schönlein purpura

Forty-six children with Henoch-Sch?nlein purpura were studied.Their clinical manifestations included palpable purpura in 100%, subcutaneous edema in 30%, arthritis/arthralgia in 78%, gastrointestinal involvement in 56% and renal abnormalities in 30%. Serum IgA was elevated in 12%, ASLO titers in 27% and microscopic hematuria and proteinuria were detected in 30% of the children, including two with nephrotic syndrome. Treatment with non-steroidal antiinflammatory drugs or corticosteroid was indicated in 43% of the children. Recurrence of the disease was observed in 22% and the prognosis seems to be related to severity of renal involvement.     

Evaluation of delta-aminolaevulinic acid excretion in random urine samples of children

Urinary delta-aminolaevulinic acid (-ALA) excretion was evaluated in random urine samples of 191 healthy children, aged 2–14 years, with blood lead levels <0.8 mol/l (mean ± SD: 0.34±0.13), erythrocyte zinc-protoporphyrin <70 mol/mol haem (mean ± SD: 50.4±8.0) and blood haemoglobin >6.8 mmol/l (mean ± SD: 8.2±0.5). It was found that uncorrected -ALA concentration and -ALA/creatinine ratio are age-dependent, whereas the ratio of -ALA/logarithm of creatinine concentration (mean ± SD: 55.3±13.5 mol/log mmol) is independent of age and sex. The authors recommend the use of this parameter for the assessment of -ALA excretion in random urine samples in children     

Hairy cell leukemia: authors' own experience (1977-1998)]

Hairy cell leukaemia (HCL) is a rare, clinically and haematologically well characterised entity. The prognosis of patients with hairy cell leukaemia has significantly improved due to the new therapeutic approaches. Development of diagnostic and therapeutic methods, together with the analysis of their own hairy cell leukaemia patients, is reviewed by the authors. Between 1977 and 1998 twenty five patients (16 male, 9 female) were treated. The malignant cells were usually analysed by morphological and cytochemical methods and recently flow cytometric analysis could be performed in eight patients. Splenectomy with lethal outcome in six patients was performed in 21 cases. Approximately one third of patients received interferon, while 2-chlorodeoxyadenosine was given only to three patients. Favourable experiences obtained by splenectomy and efficacy of interferon treatment are emphasised, but according to the literature and their own results administration of purine analogues can be highly recommended in the future.     

Adult onset Still disease: comment on two cases

The adult onset Still disease is a systemic disease of an unknown etiology. As a separate entity, it was described firstly in 1971. The diagnosis is problematic and based upon special criteria. In this study, we present the cases of two patients with adult onset Still's disease, causing several serious differential-diagnostic problems. In the beginning of the disease a high, remittent-intermittent fever was present which reacted well to salycilates. Almost simultaneously, a characteristic, confluent, no itching rash appeared on the trunk and limbs. Pain of little joints of the hands was an early symptom of the disease in both of the cases. Before the final diagnosis, the possibility of any infectious diseases, haematologic malignancies or other autoimmune disease had to be excluded. The aim of this work was to show an overall, up-to-date picture of the disease based on two typical cases.