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V Rossi

Publications and source records attributed to V Rossi.

At least 109 records · Page 6Linked to original sources
PubMed1990

Primary structure and assignment to chromosome 6 of three related rat genes encoding liver serine protease inhibitors.

Three closely related SPI genes which encode highly homologous proteins of the serine protease inhibitor family secreted by rat liver (SPI-1, SPI-2 and SPI-3), were isolated from genomic libraries and sequenced, totally (SPI-2) or partially (SPI-1 and SPI-3). These genes all map on rat chromosome 6. Each of them spans about 10 kb and contains five exons separated by four introns, located at equivalent positions. S1 mapping analysis indicated that initiation of transcription occurs at the same position (tsp) in each of the three genes. In vitro transcription experiments demonstrated the presence of promoter elements upstream from the putative tsp. Detailed analysis of 5'-flanking sequences in the three SPI revealed major differences. A high degree of identity (70%) was found within a 350-bp region preceding the 'cap' site, with the exception of a 42-bp spacer, which was only found in SPI-3. Upstream from that point, SPI-1 and SPI-2 sequences remain largely homologous over at least 1 kb but completely diverge from the corresponding sequence in SPI-3. This may, at least partly, account for the differential regulation of the three SPI observed during acute inflammation and upon hypophysectomy.

Amino Acid Sequence↗
PubMed1990

High prevalence of T-cell receptor V delta 2-(D)-D delta 3 or D delta 1/2-D delta 3 rearrangements in B-precursor acute lymphoblastic leukemias.

Rearrangement of the immunoglobulin (Ig) and T-cell receptor (TcR) genes generally has been considered a useful marker of B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangements of Ig and TcR genes have been commonly reported in the most immature lymphoid malignancies, mainly in B-cell precursor acute lymphoblastic leukemia (ALL). To better characterize the nature of this lineage promiscuity, we have analyzed the configuration of the TcR delta locus in 75 B-precursor ALL. The large majority of cases (87%) displayed a rearrangement or deletion at the delta locus. Among the 57 nondeletional rearrangements, two patterns were predominant and both appeared to derive from partial joining: a V delta-(D)-D delta 3 (32/57) and a D delta 1/2-D delta 3 (11/57) type. A single V delta gene (V delta 2) appeared to be involved in the first type of rearrangement. These findings are at variance with T-ALL, where rearrangements 5' to V delta 2 are usually found. It remains to be elucidated whether this incomplete attempt of V delta 2 gene assembly is related to the neoplastic event or represents a physiologic predisposition occurring during early stages of the normal lymphocyte differentiation.

B-Lymphocytes↗
PubMed1990

Lymphocytes of a patient with lymphoproliferative disease of large granular lymphocytes express high natural killer, ADCC, and LAK activity.

The clinical, morphological, immunological, and molecular features of a case of expansion of large granular lymphocytes (LGL) are reported. Surface marker analysis of peripheral blood and spleen mononuclear cells showed that the majority of these cells were CD3-, CD2+, CD16+, and Leu 7-. Ultrastructural characteristics of CD16+ cells revealed a low nuclear/cytoplasmatic ratio, irregularly shaped nucleus, and numerous cytoplasmatic granules. Functional studies showed reduced proliferative responses to mitogens (PHA, Con A, PWM) and high levels of natural killer (NK) activity as well as antibody-dependent cell cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activities. Molecular analysis of the T cell receptor genes revealed a germline configuration of the beta, gamma, and delta genes; however, as for normal NK cells, delta-related mRNA transcripts were found. Three months from diagnosis, the patient developed profound thrombocytopenia and splenectomy was carried out with complete normalization of the platelet counts and of hematological values while LGL lymphocytosis persisted. Although no tools are available for studying the monoclonality of CD3- lymphoproliferative disease, the clinical course, the absence of chromosomal abnormalities, and a liver histology indicative of chronic active hepatitis suggest that LGL expansion in this patient could be part of a benign, possibly reactive, process.

Adult↗
PubMed1989

T cell receptor delta gene organization and expression in normal and leukemic natural killer cells.

In peripheral blood most NK activity is mediated by CD3- cells with large granular lymphocyte morphology which cannot be assigned to a specific hemopoietic lineage. In accordance with previous studies we have analyzed the organization of the TCR delta gene, which rearranges early in thymic ontogeny, in normal NK cells, and in granular lymphocytes proliferative disorders (GLPD), in an effort to further define their relationship to the T cell differentiation pathway and to identify a possible marker of clonality for CD3- GLPD. The alpha/delta locus was rearranged in five cases of CD3+ GLPD with a biallelic deletion of the C delta region, suggesting V-J alpha rearrangement, whereas CD3- GLPD and normal CD3- NK cells had the delta gene in germ-line configuration, but surprisingly expressed high levels of TCR delta-related mRNA. On the basis of this finding and of the presence of truncated TCR-beta and CD3-epsilon mRNA, we are led to speculate on a possible ontogenic relationship of NK cells to the T cell differentiation pathway at stages preceding TCR gene rearrangement.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Chromosome size and number polymorphisms in Leishmania infantum suggest amplification/deletion and possible genetic exchange.

We have studied the molecular karyotypes of 21 strains and 14 clones of Leishmania infantum using pulsed field gel electrophoresis (PFGE). We detected a high degree of polymorphism within this species, with 'strain-specific' patterns for most isolates, even within a restricted endemic area. Variations relate to both the size of chromosomes (270-2600 kb) and their number, which can vary from 24 to 31 between closely related isolates. This polymorphism does not correlate with isoenzyme analysis. Small size variations between homologous chromosomes of different strains are suggestive of DNA amplification/deletion events. Strains are also shown to be multiclonal, with slight differences between most clones, but with a predominant clone concealing the others in PFGE analysis. The analysis of these data leads to the hypothesis of occasional genetic exchange by nuclear fusion in Leishmania, as recently shown in the related protozoan Trypanosoma brucei.

Animals↗
PubMed1989

T-cell receptor delta gene rearrangement in childhood T-cell acute lymphoblastic leukemia.

During the development of functional T lymphocytes, a variety of genes involved in antigen recognition undergo somatic rearrangement. These include the alpha, beta, and gamma chain genes. Recently a fourth rearranging gene, the delta chain gene, embedded in the alpha chain locus, has been described. We have determined the structure of the beta, gamma, and delta chain genes in 15 cases of T-cell acute lymphoblastic leukemia (T-ALL) representing stage I (CD7+, CD1-, CD3-) and stage II (CD7+, CD1+, CD3-) of intrathymic T-cell development. The alpha-delta locus was rearranged in 14 of the 15 cases. In three cases the delta constant region was deleted on both chromosomes, suggesting biallelic V-J alpha rearrangement. A limited pattern of rearrangement of the delta locus was observed in the remaining 11 cases. When the alpha-delta region was rearranged, there was rearrangement of the beta and gamma TcR in all cases except two; in these cases the beta chain was in the germline configuration. These findings support the hypothesis that delta chain gene rearrangement is an early event in T-cell development, possibly contemporary to gamma gene rearrangement, and that the delta locus has a limited repertoire.

Gene Rearrangement, T-Lymphocyte↗
PubMed1989

Methodological approach and diagnostic usefulness of a new assay for anti-thyroid peroxidase autoantibodies.

Although thyroid microsomal antibodies (anti-MAb) have been recently proven to be directly to thyroid peroxidase (TPO), current methods for MAb detection still employ unpurified microsomal fractions. The authors have therefore developed and evaluated a specific radioimmunoassay (RIA) for autoantibodies to TPO (anti-TPO Ab) based on competitive inhibition of 125I-TPO to an anti-TPO monoclonal antibody coated on plastic microtiter wells (RIA-1) or tubes (RIA-2). Preliminary experiments showed that both assays were able to specifically detect anti-TPO Ab, while negative results were obtained with normal sera and with sera containing other organ- and non-organ-specific autoantibodies including anti-thyroglobulin antibodies (anti-TgAb). No significant difference in sensitivity, specificity and reproducibility was found between RIA-1 and RIA-2, and the results obtained with the two techniques were therefore pooled together. Anti-TPO Ab were then assayed in 110 normal controls and in 441 patients with different autoimmune (AITD) or non-autoimmune (N-AITD) thyroid diseases and compared to anti-M Ab as assessed by passive hemagglutination (PH). Positive anti-TPO Ab were observed in 4/110 (3.6 p. cent) normal controls, 88/117 (80 p. cent) patients with Graves' disease, 122/123 with Hashimoto's thyroiditis or idiopathic myxedema and 21/201 (10.4 p. cent) with miscellaneous N-AITD. A highly significant positive correlation (r = 0.91, p less than 0.0001) was found between anti-MAb by PH and anti-TPO Ab by RIA ;discrepant results were limited to sera with negative or low (1/100-1/400) anti-M Ab titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1989

Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia.

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.

Animals↗
PubMed1989

Hereditary motor and sensory neuropathy type I and motor neuron disease. An unusual association.

A 34-year-old man experienced progressive muscle weakness and wasting in the shoulder girdle later spreading distally to the upper limbs. Neurological examination revealed signs of pyramidal and bulbar involvement as well as widespread fasciculations. Pes cavus and distal hypoesthesia were also observed. MCV and nerve biopsy findings were consistent with HMSN-I, while EMG pattern suggested a MND. The association of HMSN-I with MND has not been previously described in literature.

Adult↗
PubMed1988

Comparison of histone variant synthesis in human lymphocytic leukemia cells and in normal lymphocytes.

The synthesis of core histone variants and of histone H1 variants was determined in fresh leukemic cells of eight patients with leukemia [seven acute lymphoblastic (ALL) and one chronic lymphocytic (CLL)], in normal lymphocytes from healthy donors or from ALL patients in complete remission. Histone variant synthesis was evaluated by incubating cells with [14C]Lys and [3H]Arg in medium without Lys and Arg and then by two-dimensional polyacrylamide gel electrophoretic separations (acetic acid-urea-Triton x-100 acetic acid-urea-hexadecyltrimethylammonium bromide for core histone variants; sodium dodecyl sulfate/acetic acid-urea-hexadecyltrimethyl ammonium bromide for H1 variants). As previously reported, quiescent lymphocytes and lymphocytes stimulated with phytohaemagglutinin (PHA) showed clearcut changes in the proportions of synthesis of core histone variants and H1 variants. Leukemic lymphocytes freshly obtained from blood showed a pattern of core histone synthesis and H1 synthesis intermediate between that of quiescent and PHA-stimulated lymphocytes; this is probably due to the presence of a mixture of resting and growing cells. When leukemic cells were stimulated to grow by mitogens, the pattern of core histone and H1 variant synthesis was similar to that in mitogen-stimulated normal lymphocytes. Histone variants whose synthesis is associated with the S-phase were not synthesized in leukemic cells treated with the DNA synthesis inhibitors hydroxyurea and 1-beta-D-arabinofuranosylcytosine (Ara-C). The pattern of acetylation of histone H4 was also apparently similar in leukemic cells and normal lymphocytes. The radioactivity associated with the ubiquitinated forms of H2A increased in nongrowing lymphocytes and in leukemic cells treated with DNA synthesis inhibitors whereas they decreased after mitogenic stimulation. Variability was wide in the synthesis of ubiquitinated H2A in different cases of leukemia. The only clear-cut difference between leukemic cells and normal lymphocytes was that leukemic cells from ALL patients, but not lymphocytes from normal donors or from ALL patients in complete remission, synthesized appreciable amounts of H1 degrees, increasing after hydroxyurea/Ara-C treatment and decreasing after PHA-stimulation. In leukemic cells from a CLL patient H1 degrees synthesis was undetectable.

Acetylation↗
PubMed1988

Reproductive toxicity of 2,4-toluenediamine in the rat. 3. Effects on androgen-binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis.

In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.

Androgen-Binding Protein↗
PubMed1987

Correlations between embryotoxic and genotoxic effects of phenytoin in mice.

The anticonvulsant drug phenytoin (DPH) has been suspected to produce embryotoxicity through an arene oxide intermediate. This drug was also found to be a genotoxic agent. These hypotheses were tested in pregnant mice modulating the phases I and II metabolizing enzymes. DPH was studied by assessing embryotoxicity, teratogenicity, and genotoxicity, the latter by the micronucleus test on the polychromatic erythrocytes of dams and fetuses. DPH embryotoxicity was potentiated by inhibiting both cytochrome P-450 and epoxide hydrase and decreased by inducing cytochrome P-450. Equivocal results were obtained by modulating cytochrome P-448. The main DPH metabolite, p-hydroxyphenytoin (HPPH), was ineffective both per se and after cytochrome induction or epoxide hydrase inhibition. DPH did not exert genotoxicity on the maternal organism, no matter which modulating agent was used. In the fetus, however, weak genotoxic effects were observed. These effects significantly increased with inhibition of epoxide hydrase; they disappeared with induction of both cytochromes P-448 and P-450 or with inhibition of the latter. No genotoxicity was exerted by HPPH, even when the enzymatic pattern was modulated. It is concluded that the major role in DPH embryotoxicity is played by the unchanged drug, while the presence of the arene oxide is determinant for genotoxic effects.

Abnormalities, Drug-Induced↗
PubMed1987

Histone H1(0) is synthesized by human lymphocytic leukemia cells but not by normal lymphocytes.

Using a two-dimensional gel electrophoresis system (sodium dodecyl sulphate/acetic acid-urea-hexadecyltrimethylammonium bromide) coupled with fluorography, we investigated the synthesis of H1 isoproteins in leukemic cells obtained from peripheral blood of eight children suffering from acute lymphoblastic leukemia (ALL) (four T-ALL, three common ALL, and one B-ALL) and in normal peripheral lymphocytes. H1 was synthesized in leukemic cells but not in normal lymphocytes. Inhibition of DNA synthesis with hydroxyurea and 1-beta-D-arabinofuranosylcytosine induced an increase of relative synthesis of H1(0) in leukemic cells but did not induce any detectable synthesis of H1 in normal lymphocytes. H1(0) synthesis was also undetectable in peripheral lymphocytes of leukemic children in complete remission after chemotherapy and in lymphocytes of a homozygotic twin of a leukemic patient. H1(0) may be a marker of malignant transformation of lymphocytes and as such could be of use for early detection of relapse in patients with acute lymphocytic leukemia in apparent complete remission.

Electrophoresis↗
PubMed1986

Electroretinographic and visual evoked potential abnormalities in myotonic dystrophy.

Pattern visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded in 20 patients with myotonic dystrophy. Thirteen out of 20 cases presented both VEP and ERG abnormalities, 3 only ERG alterations, 2 only abnormal VEPs. A significant inverse correlation between P100 latencies and b1 wave amplitude was observed, while N1-P100 and b1 wave amplitude exhibited a parallel change. These data suggest that retinal abnormalities may have a role in inducing subclinical visual pathway alterations in myotonic dystrophy.

Adolescent↗
PubMed1986

Lymphokine production in T gamma lymphoproliferative disorders.

We have studied five patients with chronic lymphocytosis consisting of large granular lymphocytes (LGL). The increased numbers of LGL in these patients had little or no natural killer activity, mediated antibody-dependent cellular cytotoxicity, and were induced to kill tumour lines after culture for 3 days with interleukin 2 (IL-2). Patients' LGL showed considerable reactivity with HNK-1 and AB8.28 monoclonal antibodies (MoAb), whereas positivity for OKM1 and N901 was found in only two subjects, and only one patient reacted with B73.1. No appreciable reactivity has been found with anti-Tac MoAb in the four patients tested. In the absence of stimulation, the patients' LGL produced no IL-2 and only minimal amounts of IL-1 and interferon (IFN). On stimulation with lipopolysaccharides (for IL-1) or phytohaemagglutinin A (PHA) (for IL-2 and IFN), they produced IL-1 and IFN in amounts similar to those produced by normal lymphocytes, but only modest levels of IL-2. These results indicated that proliferating LGL, like normal LGL, have a secretory capacity. The lack of constitutive lymphokine production, the lack of Tac receptor expression, and the defect in IL-2 production after PHA stimulation do not support the hypothesis of an autocrine proliferation sustained by a known growth factor.

Adult↗
PubMed1986

Role of interleukin-1 in the depression of liver drug metabolism by endotoxin.

Endotoxin-resistant C3H/HeJ mice were used to test the hypothesis that a macrophage product, possibly interleukin-1, might mediate the depression of liver cytochrome P-450-dependent drug metabolism in endotoxin-treated mice. Depression of liver drug metabolism by endotoxin was observed in normal mice (C3H/HeN) but not in C3H/HeJ mice. Serum transfer experiments demonstrated that a serum factor was responsible for the depression of liver drug metabolism. Experiments of passive transfer of peritoneal macrophages showed that this endotoxin-induced factor might be a macrophage product. In vitro experiments showed that endotoxin-stimulated monocytes produced a factor that depressed cytochrome P-450-dependent metabolism in cultured hepatocytes. Homogeneous human monocyte and recombinant interleukin-1 also depressed liver drug metabolism both in vivo and in vitro, suggesting that this macrophage product might be involved in the regulation of liver function by the immune system.

7-Alkoxycoumarin O-Dealkylase↗