The expression of the gut intra-epithelial T-cell associated molecule HML-1, a trimeric protein of 150, 125, 105 kD, was studied in 75 T-cell lymphomas of different subtypes: 20 T-lymphoblastic ...lymphomas/leukaemias; 50 nodal peripheral T-cell lymphomas; and five intestinal T-cell lymphomas. Our results confirm: (i) the usefulness of the HML-1 monoclonal antibody as an immunohistochemical marker for intestinal T-cell lymphomas: and (ii) the lack of reactivity of HML-1 with nodal peripheral T-cell lymphomas. Moreover, expression of the HML-1 molecule was found for the first time in a case of T-lymphoblastic lymphoma/leukaemia. The patient presented with a mediastinal mass which consisted of HML-1 + neoplastic cells displaying a phenotypic profile consistent with early thymocytes. Genes coding for the alpha, beta, gamma and delta chains of the T-cell receptor were in a germline configuration. The neoplastic cells could have been derived from the small subset of HML-1 + thymocytes detectable in the cortex of normal human thymus.
Extended X-ray absorption fine structure spectroscopy has been used to investigate the microscopic structure of InGaAs pseudomorphically grown on a < 001 > GaAs substrate. The measure is restricted ...to the quasi-surface region of the epitaxial growth by means of the glancing-angle technique. The results show that the strain is accommodated by bond-stretching and bond-bending and that the lattice expands in the growth direction within the limits previewed by the elastic theory.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mice with megakaryocytic-targeted ablation of GATA-1 expression (GATA-1low mice) develop while age a syndrome similar to idiopathic myelofibrosis. These mice present with life-long thrombocytopenia ...and extensive proliferation of differentiation-impaired megakaryocytes. Although GATA-1 affects erythroid cell production, GATA-1low mice are not anemic because of increased erythropoiesis in the spleen. At 8–10-month, GATA-1low mice develop anemia, osteosclerosis, marrow and spleen fibrosis and neoangiogenesis. From 15-month, extensive extramedullary hematopoiesis in the liver occurs. Myelofibrosis is developed by hemizygous male and heterozygous females alike. In order to evaluate the role of the spleen in the development of extramedullary hematopoiesis, young (6-month) wild-type littermates (WT) and GATA-1low mice (both hemizygous males and heterozygous females) were splenectomized. Three- and 9–12 months later, the myelofibrotic trait expressed by the treated animals was compared with that of un-manipulated controls. Although all the mice survived surgery, a dramatic difference in mortality was observed between hemizygous males, which died of severe anemia within 2-weeks, and heterozygous females (no death recorded). Heterozygous GATA-1low females developed a modest anemia 9–12-months after surgery (Htc, 40.1±2.7% vs. 48.2±5.5 in splenectomized GATA-1low and WT littermates, respectively, p<0.01), comparable to that presented by the age-matched untreated mutants. Platelet counts increased 2-to-3-fold in both WT and GATA-1low mice, but remained significantly lower than normal in the latter. There was an increase in the number of CD16+ NK cells in the blood of splenectomized GATA-1low mice (287±61 vs. 61±19 CD16+ cells/mL in splenectomized GATA-1low and WT littermates, respectively), but no other abnormality in blood cell counts was observed. At 3 months post-splenectomy, the number of bone marrow cells in GATA-1low mice increased up to normal from 4.0(±1.2)x106 to 8.0(±1.3)x106 cells/femur in untreated and splenectomized mutants, respectively. Histologic evaluation of bone sections showed no overt change in the extent of marrow fibrosis compared to age-matched untouched mutants, while the extent of trabecular bone was reduced. No fibrosis developed in WT mice at any time point after splenectomy, nor were changes in total marrow cellularity observed. There was no sign of extramedullary hematopoiesis at 3 month post-splenectomy in either WT or GATA-1low mice, while at the later time point, mutant mice showed a prominent involvement of the liver with high numbers of megakaryocytes, isolated or in clusters, and maturing cells of all hematopoietic lineages, that in extreme cases diffusely infiltrated the parenchyma. Extramedullary hematopoiesis was not found in either the lung or the kidney. In conclusions, splenectomy affected the extent but not the timing of the development of extramedullary hematopoiesis in GATA-1low mice suggesting that the number of stem cells present in the marrow of old splenectomized animals was sufficient to colonize the liver. The observation that splenectomy per se does not result in extramedullary hematopoiesis support the hypothesis that it is not fibrosis of the spleen, but a second hit within the stem cell compartment, that is possibly responsible for the development of extramedullary hematopoiesis in this mouse model of myelofibrosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatitis E virus (HEV) is the causative agent of Hepatitis E. Swine and human HEV strains are genetically related, suggesting the occurrence of zoonotic transmission. Recently, in Japan, cases of ...food-borne HEV transmission have been described in people after consuming raw or undercooked meat from wild boars or pigs. Although, swine HEV strains have been detected in pig herds in many European countries, only minimal information is presently available about the circulation and the prevalence of HEV in wild boars in Europe. In this study, we investigated the presence of HEV in a demographic managed wild boar population in Italy. Detection of HEV RNA was accomplished using a nested reverse-transcription polymerase chain reaction on bile samples from 88 shot animals. HEV RNA was detected in 22 out of 88 animals tested (25%). Phylogenetic analysis on the nucleotide sequences obtained from 10 positive PCR products indicated that only one HEV strain was circulating in the wild boar population considered, and that this strain was closer to human and swine HEV strains circulating in Europe than to wild boar Japanese strains.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody ...titers of the IgG or IgA classes, and no bactericidal activity in vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.
Thirteen hairy-cell leukaemia patients were treated with IFN-beta (6 X 10(6) IU/m2) for 7 days, alternate weeks, for three cycles. IFN-beta was then continued at the same dose twice a week for 24 ...weeks. Treatment was discontinued in 2 non-responders and 2 partial responders (1 haem PR, 1 path PR) because of complications unrelated to IFN. The objective response in the nine patients who completed therapy was 66% (1 CR, 3 path PR and 2 haem PR); 2 patients achieved MR. Responses lasted from 5 to 45+ months. Four newly diagnosed patients and 3 in relapse after discontinuation of IFN-beta therapy (6 X 10(6) IU/m2), were treated with a lower dose of IFN-beta (2 X 10(6) IU/m2). The objective response to this dose was 57% (3 path PR, 1 haem PR). Another patient obtained MR. No patient has relapsed 6-12 months after therapy discontinuation. IFN-beta was well tolerated, especially at the lower dose and no chronic toxicity was observed. Therefore IFN-beta may be suggested as an alternative treatment for HCL.
Three cases of idiopathic myelofibrosis with partial trisomy of the long arm of chromosome 1 are described. Partial trisomy 1q was the only karyotypic change detectable in unstimulated peripheral ...blood cell cultures of one and bone-marrow cultures of two patients at diagnosis. The extra segment from chromosome 1 was located on different karyotype sites, i.e. 1qter, 1p34 and 6p22-23; 1q21-32 was the shortest overlapping region and the only trisomic segment in one of the three patients. These findings suggest that partial trisomy 1q is a primary chromosome aberration in myelofibrosis relevant in the pathogenesis of this hematologic disorder.
Recent studies in gene transfer suggest that the innate immune system plays a significant role in impeding gene therapy. In this review, we examine factors that might influence the recruitment and ...activation of the innate system in the context of gene therapy. We have adopted a novel model of immunology that contends that the immune system distinguishes not between self and nonself, but between what is dangerous and what is not dangerous. In taking this perspective, we provide an alternative and complementary insight into some of the failures and successes of current gene therapy protocols.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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