[Chronic lymphatic leukemia and large granular lymphocytes]. / Leucemia linfatica cronica a grandi linfociti granulari.

Chronic large granular lymphocyte leukemia is a rather rare disorder (less than 5% of LLC). Its subtype CD3+/CD8+ is often a clonal disease and without malignant characteristics. This kind of disease shows a clinical and laboratory heterogeneity, probably due to the immunological and functional variety of granular lymphocytes. In some cases of LGL leukemia an associated pathology, especially rheumatoid arthritis and chronic infections, has been reported. On the contrary, the relationship with neoplasms has been rarely proved in literature: only occasional studies have been reported and anyway they are not supported by a sufficient number of cases. Two cases of LGL leukemia are here delineated: a woman with advanced breast adenocarcinoma and another one with Sjögren disease. The first one had a rapidly fatal course, while the other one had a prolonged clinical course with chronic neutropenia (13 years follow-up). The association between carcinoma and LGL leukemia may be just a casual finding but the hypothesis of a possible relationship is however very interesting on account of the important role of granular lymphocytes in controlling tumoral growth. Moreover, both patients had concomitant chronic HCV-correlated infection: maybe it will worth making a prevalence study with a greater number of cases, in order to evaluate a probable relationship between these pathologies. The growth factor G-CSF may be useful in the treatment of infections that often occur in patients with severe neutropenia.

Molecular analysis of HTLV-I and HTLV-II isolates from Italian blood donors, intravenous drug users and prisoners.

Using molecular methods three or five major variants of HTLV-I have been identified; moreover two subtypes of HTLV-II defined as HTLV-IIa and HTLV-IIb with six variants within each of these groups have been described. In the present study we analysed proviral DNA obtained from the peripheral blood mononuclear cells (PBMCs) of a significant group of Italian intravenous drug users (IVDUs), prison inmates and blood donors (BDs) who were HTLV antibody positive. Restriction fragment length polymorphism (RFLP) of amplified LTR region with ApaI, NdeI, DraI, SacI and MaeIII endonucleases was used to define the HTLV-I subtypes, while the different variants of HTLV-IIa and -IIb were defined by RFLP of the LTR region with the AvaII, BglI, SauI, XhoI and BanII endonucleases. The four HTLV-I isolated from BDs were characterized as C type. All the 11 HTLV-II detected in the IVDUs were HTLV-IIb4, while among the prisoners one HTLV-IIb5 and five HTLV-IIb4 were found. Interestingly, in the BDs group two HTLV-IIa0 and one HTLV-IIb4 were detected. It should also be noted that 82% of the IVDUs and 50% of the prisoners were coinfected with HIV, while all the BDs were HIV negative. These data indicate that HTLV-IIb4 is the predominant genotype in Italian IVDUs and prisoners, while the significant variability observed in the BD HTLV-II isolates could be due to the different source of infection among this group.

Human T-cell lymphotropic virus tax and Epstein-Barr virus DNA in peripheral blood of multiple sclerosis patients during acute attack.

OBJECTIVES: A study was performed to determine whether persistent or latent viruses are reactivated during the acute attack in relapsing remitting multiple sclerosis (MS). MATERIAL AND METHODS: DNA of herpes simplex virus type 1 and 2 (HSV-1 and -2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), JC virus (JCV) and HTLV-I was searched, using nested polymerase chain reaction (PCR), in peripheral blood mononuclear cells (PBMCs) collected from 14 MS patients on the first day and, twice a week, during an acute attack of the disease. RESULTS: Viral DNA was detected, in at least one PBMC sample, in all the patients. Interestingly, EBV DNA was found in 42.8% of the patients on the first day, while a sharp increase of the HTLV tax-rex DNA frequency (35.7%) was observed on the tenth day. CONCLUSIONS: In MS relapse EBV DNA detection is an early, frequent event, while the finding of tax-rex, but not of other HTLV-I genomic regions, is a secondary phenomenon, suggesting that these two factors could interact in the pathogenesis of MS relapses.

[Angiogenesis and antitumor therapy]. / Angiogenesi e terapia antitumorale.

We have examined the most recent literature dealing with the relationship between tumor growth and neovascularization (tumoral neoangiogenesis). It is quite evident that antiangiogenic therapy against solid tumors has an important theoretical basis. Many antiangiogenic substances are presently under study, and some inhibitors of angiogenesis, such as TNP-740, platelet factor 4, linomide, tecogalan, etc., are currently being tested in phase 1 or 2 clinical trials. These studies have, however, underscored the possibility of numerous side effects due to the lack of specificity of these substances against endothelial cells. The most promising and rational use of antiangiogenic factors in anticancer therapy seems to be their association with traditional chemo- or radiotherapy. Gene therapy also offers considerable theoretical promise as demonstrated by the transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line.

HTLV tax-rex DNA and antibodies in idiopathic amyotrophic lateral sclerosis.

In an attempt to verify the possible role of retrovirus in idiopathic amyotrophic lateral sclerosis (ALS), the sera of 21 ALS patients admitted to the Neurological Unit of the Don Gnocchi Foundation in Milan, Italy, and of 9 ALS patients from Ulm University in Germany have been evaluated for the presence of antibodies to the human T-lymphotropic viruses (HTLV-I and HTLV-II). The sera of 30 healthy individuals and 20 HIV-infected but HTLV-negative subjects have been also studied as control. Moreover, the HTLV tax-rex and pol DNA sequence have been searched in the peripheral blood mononuclear cells (PBMCs) of 15 ALS patients and 15 HIV-positive HTLV-negative subjects using a nested PCR currently employed in our laboratory for the study of HTLV infections. Antibodies to one or more HTLV proteins have been found by using a Western blot (WB) kit in the sera of 10 Italian and 7 German ALS cases, while all the healthy controls were negative and only one HIV-positive subject had antibodies to HTLV gp21. HTLV tax-rex sequences have been found in the PBMCs of 6 ALS patients while all the controls were negative. All 15 ALS cases and controls were negative for HTLV pol DNA indicating that only the most conserved region of the HTLV genome could be detected. On the whole our data indicate that some ALS patients have antibodies to HTLV proteins and that the tax-rex region of the HTLV genome can be found in their PBMCs.