bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polycythaemia vera in young people: an analysis of 58 cases diagnosed before 40 years
Authors: Najean Yves , Mugnier Pascale , Dresch Catherine , Rain Jean‐Didier 
Published: July 2010

SummaryOver 20 years, 58 cases of PV in young people (46 meeting the full PVSG criteria, 12 with elevated red cell volume and leucocytosis or thrombocytosis, without splenomegaly) were studied and have been followed for periods of 3–24 years. These cases represent approximately 5% of the cases of PV referred to the Department of Nuclear Medicine of St Louis Hospital during this period. They differ from older patients in the initial clinical severity, the short interval between the first symptoms and the diagnosis, frequent presentation with a life‐threatening complication (two cases of hepatic vein thrombosis, six thrombotic or haemorrhagic events, six splenectomies, two abortions) and a very enlarged spleen in half the cases. However, after the initial complications, the overall survival is very long (exceeding 70%, even when including the initial complications, at 15 years).The vascular accidents occur exclusively in the phlebotomized patients, the main risk factor being the poor stability of the haematocrit. Only one acute leukaemia was observed among the 14 cases treated by radioactive phosphorus and/ or alkylating chemotherapy. The most frequent late complication was evolution towards myelofibrosis. This spent phase seemed to occur earlier in patients treated by phlebotomy.On the basis of this data, we would advise the following therapeutic strategy: phlebotomies, as soon as the diagnosis is established, and a systematic long‐term treatment by hydroxyurea with the hope of reducing the number of vascular complications and of delaying the evolution towards the spent phase and the myelofibrosis.
Aberrant expression of immunoglobulin light chain isotype in B lymphocytes from patients with monoclonal gammopathies: isotypic discordance and clonal B‐cell excess
Authors: Oritani Kenji , Katagiri Shuichi , Tominaga Nobuhiko , Iida Masato , Amano Toshio , Karasuno Takahiro , Matsumura Itaru , Mitsui Hideki , Kanayama Yoshio , Yonezawa Takeshi , Tarui Seiichiro 
Published: July 2010

SummaryA study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B‐cell differentiation, namely, circulating surface Ig positive (SIg +) cells, Ig‐secreting cells (plaque forming cells, PFC) and mitogen‐induced PFC. By using kappa‐lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B‐cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen‐induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B‐cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P<0.02). ID and CE can therefore be considered as useful markers for discriminating between MGUS and myeloma, evaluating the clinical stability and predicting the clinical course.
Megakaryocyte maturation is associated with expression of the CXC chemokine connective tissue‐activating peptide CTAP III
Authors: Deutsch Varda , Bitan Menachem , Friedmann Yael , Eldor Amiram , Vlodavsky Israel 
Published: July 2010

Connective tissue‐activating peptide III (CTAP III), a CXC chemokine derived from the chemokine precursor platelet basic protein (PBP) by proteolytic cleavage, has been identified in platelets, activated macrophages, neutrophils and T lymphocytes. CTAP III can support stem cell‐derived haematopoiesis yet inhibits the proliferation of committed megakaryocyte (MK) progenitors. This investigation was aimed at characterizing CTAP III expression in human MKs and determining it's role in MK differentiation. We report high expression of CTAP III in mature human bone marrow (BM) MKs and megakaryoblast cell lines following differentiation induction with phorbol ester 12‐myristate 13‐acetate (PMA). Immunostaining with anti‐CTAP III antibodies demonstrated its prominent presence in platelet producing zones in the cytoplasm and intense staining around the periphery of the large BM MKs. In cultures of logarithmically growing megakaryoblast cell lines DAMI, CHRF‐288 or MEG01, which contain primarily 2N cells, only 15% of the cells expressed CTAP III. The addition of PMA stimulated high levels of CTAP III after 24 h in more than 75% of the cells, being expressed in both the 2N and large polyploid MKs. Reverse transcription polymerase chain reaction (RT‐PCR) revealed upregulation of CTAP III mRNA after only 1 h of exposure to PMA that was sustained for 24 h. In the bone marrow of idiopathic thrombocytopenic pupura (ITP) patients undergoing accelerated MK maturation and thrombopoiesis, 99% of large MKs and 95% of small MKs expressed high levels of CTAP III. While the biological function of this chemokine in MKs is not known, these studies demonstrate that molecular upregulation of CTAP III in MKs is associated with maturation and, as with other chemokines, may be involved in proliferation arrest and cellular interactions with extracellular matrix and platelet production.
Thalidomide maintenance following high‐dose therapy in multiple myeloma: a UK myeloma forum phase 2 study
Authors: Feyler Sylvia , Rawstron Andy , Jackson Graham , Snowden John A. , Cocks Kim , Johnson Roderick J. 
Published: July 2010

SummaryThalidomide maintenance has unresolved issues regarding dosage and toxicity. We evaluated this in five dose cohorts in 100 patients. At a median follow‐up of 32·3 months, 23 patients had stopped thalidomide for disease progression, 54 for side effects. 3‐year overall and progression‐free survival was 76% and 41% respectively. Dosage did not influence disease outcome but greatly affected toxicity. Fifteen patients converted from partial remission to complete remission on thalidomide at a median of 13·5 months. Maintenance doses >200 mg were largely unachievable and peripheral neuropathy was the main toxicity. Lower doses enabled more patients to stay on the drug for a useful period of time.
Efficacy and tolerability of high‐dose methotrexate in central nervous system positive or relapsed lymphoproliferative disease following liver transplant in children
Authors: Taj Mary M. , Messahel Boo , Mycroft Julie , Pritchard‐Jones Kathy , Baker Alistair , Height Susan , Hadzic Nedim , Pinkerton C. Ross 
Published: July 2010

SummaryChildhood post‐transplant lymphoproliferative disease (PTLD) is a heterogeneous condition in which treatment varies, from the reduction of immunosuppression to moderately intensive chemotherapy. While low‐dose chemotherapy/rituximab has been found to be effective, moderately intensive chemotherapy is required for patients who relapse, have classic non‐Hodgkin lymphoma or have fulminant PTLD. Methotrexate (Mtx) is highly effective in lymphomas and crosses the blood‐brain barrier. However, there are no data in the literature regarding its safety in post‐liver transplant patients. We describe four cases of high‐grade lymphomas (three diffuse large B cell and one T‐cell lymphoblastic), post‐liver transplant, for which chemotherapy including high‐dose Mtx (HDMTX) was the treatment of choice. In total, 20 doses of HDMTX (1–5 g/m2) were given. The treatment was well tolerated and all four patients had a good response. One case of central nervous system (CNS) diffuse large B‐cell lymphoma was treated with HDMTX alone. We conclude that, in the absence of significant organ damage, HDMTX can safely be given to liver transplant patients, but should only be administered in specialist oncology units. Proof of effectiveness as a single agent in CNS lymphoma needs further studies.
The human side of hypoxia‐inducible factor
Authors: Smith Thomas G. , Robbins Peter A. , Ratcliffe Peter J. 
Published: July 2010

SummaryWhen humans are exposed to hypoxia, systemic and intracellular changes operate together to minimise hypoxic injury and restore adequate oxygenation. Emerging evidence indicates that the hypoxia‐inducible factor (HIF) family of transcription factors plays a central regulatory role in these homeostatic changes at both the systemic and cellular levels. HIF was discovered through its action as the transcriptional activator of erythropoietin, and has subsequently been found to control intracellular hypoxic responses throughout the body. HIF is primarily regulated by specific prolyl hydroxylase‐domain enzymes (PHDs) that initiate its degradation via the von Hippel‐Lindau tumour suppressor protein (VHL). The oxygen and iron dependency of PHD activity accounts for regulation of the pathway by both cellular oxygen and iron status. Recent studies conducted in patients with rare genetic diseases have begun to uncover the wider importance of the PHD‐VHL‐HIF axis in systems‐level human biology. These studies indicate that, in addition to regulating erythropoiesis, the system plays an important role in cardiopulmonary regulation. This article reviews our current understanding of the importance of HIF in human systems‐level physiology, and is modelled around the classic physiological response to high‐altitude hypoxia.
Detection of tumour necrosis factor/cachectin in pleural effusion of patients with lung cancer
Authors: ISHII Y , UCHIYAMA Y , HASEGAWA S , KINOSHITA T , MITSUI K , KOJIMA H , FUJITA T 
Published: July 2010

SUMMARY
We have found that the pleural effusion obtained from a patient with lung cancer (adenocarcinoma) has cytotoxic activity against the patient's lung cancer cells. This finding occurred in the course of establishing a lung cancer cell line from the patient's pleural effusion. The cytotoxic factor was partially purified from the pleural effusion and characterized. It had cytotoxicity against L-929 mouse fibroblasts in the standard 18-h killing assay of tumour necrosis factor (TNF). By molecular sieving chromatography, the activity appeared at molecular weight of 50 000. This activity was completely blocked by a monoclonal antibody to TNF. From these results, we conclude that the cytotoxic factor in the pleural effusion is TNF. The concentration of TNF in the pleural effusion was 34.5 pg/ml by radioimmunoassay. In addition, we detected TNF activity and protein in two other cases of carcinomatous pleural effusion. Therefore, it would appear that in vivo TNF displays cytotoxic activity against cancer cells.
Neonatal myasthenia gravis: antigenic specificities of antibodies in sera from mothers and their infants
Authors: TZARTOS S J , EFTHIMIADIS A , MOREL E , EYMARD B , BACH J-F 
Published: July 2010

SUMMARYTransient neonatal myasthenia gravis (MG) is a human model or passively transferred MG, In an effort to understand the characteristics of the most pathogenic antibodies in MG, we studied the fine antigenic specificities of anti-AChR antibodies in sera from 21 MG mothers (nine of which had transiently transferred the disease) and 17 of their infants. Although in a few cases significant differences in antibody specificities were observed between mothers and infants, whether myasthenic or not, generally the antigenic specificities of the antibodies in sera from infants were very similar to those of their mothers. Furthermore, no characteristic differences were detected between the antibody repertoires of mothers who transferred the disease and those who did not.
Distribution of the MHC antigens after liver transplantation: relationship with biochemical and histological parameters
Authors: ROUGER P , GUGENHEIM J , GANE P , CAPRON-LANDEREAU M , MICHEL F , REYNES M , BISMUTH J 
Published: July 2010

SUMMARY
The aim of this study was to analyse the change in tissue distribution of HLA class I and class II molecules in patients during the course of liver transplantation. Sixty-one liver biopsies were analysed in 24 patients with or without rejection (acute or chronic) episode. In 93% of cases with chronic rejection and in 48% of cases with acute rejection episodes, HLA class I antigens are expressed in the membrane and/or the cytoplasm of hepatocytes. The expression of these molecules was significantly correlated with the ASP (aspartate amino transferase), AP (alkaline phosphatase), the bile duct damage and the centrolobular lesions. In contrast, the expression of HLA class II molecules is not correlated with either the type of rejection, the biological or histological findings. A strong expression of HLA class I antigen on hepatocytes after day 60 may be one of the best signs of chronic rejection.
Jacalin: a lectin mitogenic for human CD4 T lymphoctyes
Authors: PINEAU N , AUCOUTURIER P , BRUGIER J C , PREUD'HOMME J L 
Published: July 2010

SUMMARYThe major protein component of seeds from jackfruit is the lectin jacalin. Jackfruit crude extracts are known to stimulate human lymphocytes, but the mitogenic properties of purified jacalin have not been studied in detail so far. Study of the proliferative response of cell populations from normal human peripheral blood to purified jacalin showed it to be mitogenic through an interaction with lymphocytes by its lectin-binding site, as shown by inhibition by IgA. Jacalin failed to stimulate B cells to proliferate and to undergo plasma cell maturation. It induced a proliferation of CD4 (and not CD8) lymphocytes, as shown by phenotypic analysis of cells recovered after culture and by studies of the response of isolated T cell subpopulations. The proliferative response to jacalin was autologous monocyte-dependent. The kinetics of jacalin-induced DNA synthesis, expression of CD25 and interleukin-2 secretion was shifted by comparison with that induced by phytohaemagglutinin. The reason for the restricted responsiveness of CD4T cells is presently unclear; jacalin bound to all blood cells and did not significantly co-cap with CD1, CD2, CD3, CD4, CD8 and CD38, and jacalin response was neither enhanced nor inhibited by antibodies to these surface antigens.
Cytokine regulation of human monocyte interleukin-1 (IL-1) productionin vitro. Enhancement of IL-1 production by interferon (IFN) gamma, tumour necrosis factor-alpha, IL-2 and IL-1, and inhibition by IFN-alpha
Authors: DANIS V A , KULESZ A J , NELSON D S , BROOKS P M 
Published: July 2010

SUMMARYIL-1 production (secreted and cell-associated) was measured in monocyte cultures stimulated by a variety of agents in vitro. Monocytes either adherent to conventional plastic culture plates in serum-free conditions, or in suspension in culture medium containing serum were stimulated to produce IL-1 during culture. In non-adherent, serum-free conditions, monocytes produced very low or undetectable amounts of IL-1 during 20 h of culture. Lipopolysaccharide (LPS) induced equivalent amounts of secreted and cell-associated IL-1, although at very low concentrations more cell-associated IL-1 was produced. IL-1 production in response to LPS could be augmented by crude lymphokine, IFN-γ, or tumour necrosis factor (TNF) alpha. TNF-α preferentially augmented the production of cell-associated IL-1 in LPS-stimulated cultures. TNF-α induced a significant amount of IL-1 (mainly cell-associated) directly but could also induce IL-1 secretion when combined with IL-2 or IFN-γ, or when in the presence of serum. IL-2 acted synergislically with low concentrations of IFN-γ or IL-1 to induce significant levels of IL-1 production. IFN-α did not induce any IL-1 production, but was a potent inhibitor of IL-1 production induced by a variety of stimuli. These results suggest that IL-1 production may be enhanced or reduced by different cytokines at concentrations likely to be found in chronic inflammatory lesions.
Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat-shock protein
Authors: YANG X-D , GASSER J , FEIGE U 
Published: July 2010

SUMMARYAdjuvant arthritis in Lewis rats is a model of T cell-mediated autoimmune arthritis resembling human rheumatoid arthritis. A nonapeptide from the 65-kD heat-shock protein of Mycobacterium bovis BCG, amino acid sequence 180–188, has been described to carry the dominant immunogenic epitope(s) for both arthritis-protective and arthritogenic T cell clones. Here we demonstrate that immunizations with the synthetic nonapeptide completely protected rats against adjuvant arthritis induced by M. tuberculosis. Interestingly, deletion of the N-teminal threonine of the nonapeptide resulted in loss of the protective activity. Pretreatments with the nonapeptide resulted in an immune response to the nonapeptide and to M. tuberculosis. After immunizations with the synthetic nonapeptide, only low titres of nonapcptidc-spccific antibodies were produced, whereas a significant cellular immune response to the nonapeptide was observed. In addition, the protection was transferable to naive rats by spleen T cells. These findings document the requirement of a T cell-specific immune response to the dominant epitope of the 65-kD mycobacterial heat-shock protein for the protection against adjuvant arthritis and suggest the feasibility of immune intervention in autoimmune arthritis through the use of synthetic peptides.
Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection
Authors: ALLOUCHE M , LUNARDI-ISKANDAR Y , VARELA-MILLOT C , ITZHAKI M , CORNUET P , MEYER P , JASMIN C , GEORGOULIAS V 
Published: July 2010

SUMMARYWe and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 × 104 cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infccted patients. However. CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients’ cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PH A + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.
Natural killer cell activity during measles
Authors: GRIFFIN D E , WARD B J , JAUREGUI E , JOHNSON R T , VAISBERG A 
Published: July 2010

SUMMARYNatural killer cells are postulated to play an important role in host anti-viral defences. We measured natural killer cell activity in 30 individuals with acute measles (73 ± 21 lytic units (LU)/107 cells) and 16 individuals with other infectious diseases (149 ± 95 LU) and found it reduced compared with values for adults (375 ± 70 LU; P&lt;0.001) or children (300 ± 73 LU, P&lt;0.01) without infection. Reduced natural killer cell activity was found in measles patients with (84 ± 30 LU) and without (55 ± 18 LU) complications and was present for at least 3 weeks after the onset of the rash. Activity was increased by in vitro exposure of cells to interleukin-2. Depressed natural killer cell activity parallels in time the suppression of other parameters of cell-mediated immunity that occurs during measles.
Evidence that the Fc region of autologous rabbit IgG isolated before and after hyperimmunization is structurally different: recognition by rheumatoid factor and monoclonal antibodies
Authors: MURRAY J S , BROWN J C 
Published: July 2010

SUMMARYAutologous hyperimmune (HI) and pre-inoculation (PI) rabbit Fcγ populations were found to be conformationally different by spectroscopic measurements, and antigenically different by measurements which examined rheumatoid factor (RF) and monoclonal antibody (MoAb) binding specificity for both populations in ELISA. Circular dichroism spectra of HI rabbit Fcγ (prepared from animals after hyperimmunization with streptococcal vaccine) were both qualitatively and quantitatively different, particularly in the 225–228 nm range, in comparison to both homologous normal and autologous PI Fcγ. Binding studies in ELISA showed that affinity constants obtained for reactions of both rabbit RF and various murine MoAb with HI IgG and Fc were approximately 10-fold higher relative to those observed for PI IgG and Fc. Enzymatic deglycosylation of HI and PI Fcγ led to elimination of CD spectral differences. Further, association constants obtained for RF and MoAb reactions with deglycosylated (sialic acid and galactose removed) PI Fcγ were equivalent to those obtained in the presence of untreated HI Fcγ. Together, these results suggest the complex oligosaceharide structure of rabbit IgG may play a significant role in the expression of Fcγ determinants, and alteration of this structure under hyperimmune or other conditions may be related to induction of an RF response.
Immune studies in infants with congenital syphilis
Authors: SAMSON G R , BEATTY D W , MALAN A F 
Published: July 2010

SUMMARYSeventeen neonates with congenital syphilis were studied to determine the immune response of the fetus following intra-uterine infection with Treponema pallidum. The results were compared with those from healthy controls matched for gestational age, birth weight and sex. B cells, IgM, and circulating immune complexes were significantly elevated in the infected newborns. There were no differences in lymphocyte transformation to phytohaemagglutinin (PHA) and in the CD3, CD4, and CD8 lymphocytes between infants with congenital syphilis and controls. Newborns with congenital syphilis have a heightened humoral response but no quantitative abnormality in cell-mediated immunity. Speculation on the role of the circulating immune complexes is presented.