bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of refractory anaemia with p53 point mutation at codon 249 (AGG to ATG)
Authors: Kikukawa Masayuki , Aoki Naoto , Mori Mayumi 
Published: November 2003

Although mutations of the p53 tumour‐suppressor gene have been observed occasionally in the advanced stages of myelodysplastic syndromes (MDS), they have not been detected in early refractory anaemia (RA) or RA with ring sideroblasts phases.Using single‐strand conformation polymorphism analysis and direct sequencing, we searched for p53 mutations in a patient who progressed from RA to overt leukaemia. A p53 mutation at codon 249 (AGG to ATG) was observed in RA, RA with excess of blasts in transformation and overt leukaemia.We describe a case of MDS with p53 mutation at codon 249 detected in the RA phase.
Mycosis fungoides and Sezary syndrome are not associated with HTLV‐I infection: an international study
Authors: Bazarbachi A. , Soriano V. , Pawson R. , Vallejo A. , Moudgil T. , Matutes E. , Peries J. , Molina A. , De The H. , Schulz T. F. , Catovsky D. , Gill P. S. 
Published: November 2003

Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T‐cell lymphotropic virus type‐I (HTLV‐I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T‐cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV‐I infection markers. HTLV‐I and ‐II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT‐PCR‐based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short‐term culture and 68 from skin lesions) by PCR amplification using HTLV‐I and ‐II gag, pol, env, pX and LTR specific primers.Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV‐I and ‐II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short‐term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV‐I infection.
Interferon-gamma (IFN-γ) down-regulates the rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) on human airway epithelial cells
Authors: SETHI S K , BIANCO A , ALLEN J T , KNIGHT R A , SPITERI M A 
Published: November 2003

SUMMARY
Human rhinoviruses (HRV) are a major cause of upper respiratory tract infections in man, and can exacerbate existing pulmonary disease. The major group of HRV attach to ICAM-1, which is expressed on nasal and bronchial epithelial cells. To study the influence of biological mediators on ICAM-1 expression, and consequently HRV attachment and infection, we compared the effects of various cytokines, alone and in combination, on ICAM-1 expression by an uninfected and HRV-infected bronchial epithelial cell line H292. Cytokines known to be released soon after viral infection, such as tumour necrosis factor-alpha (TNF-α), IL-1β and the chemokine IL-8 increase ICAM-1 expression on uninfected cells. Epithelial cells infected with live HRV-14 displayed marked up-regulation of ICAM-1 compared with baseline. TNF-α further enhanced the HRV-induced increase in ICAM-1 expression on epithelial cells, peaking at day 4 after infection, whilst IL-8 exhibited a steady increase in ICAM-1 expression over 14 days. In contrast, IFN-γ, a known Th1 antiviral lymphokine, whilst increasing the level of ICAM-1 on uninfected cells, induced a significant persistent down-regulation of ICAM-1 expression on HRV-infected epithelial cells. With combinations of TNF-α and IFN-γ, ICAM-1 expression on HRV-infected cells was reduced to basal levels. The effects of IFN-γ were paralleled by a reduction in viral titres. Our in vitro model has provided useful insights into the early pathogenic events of HRV infection at the level of the host cell–virus interaction. Our data confirm that biological mediators play a crucial role in the pathogenesis as well as the course of HRV infection which is modulated by the types, and time kinetics of inflammatory cytokines in the immediate microenvironment.
Humoral immune response within the lung in HIV-1 infection
Authors: MOJA P H , JALIL A , QUESNEL A , PEROL M , COTTE L , LIVROZET J M , BOIBIEUX A , CHAMSON A , VERGNON J M , LUCHT F , TRAN R , POZZETTO B , GENIN C 
Published: November 2003

SUMMARY
In order to study the humoral immune defences in the respiratory tract during HIV-1 infection, we measured the levels, local productions and anti-HIV and antibacterial activities of IgG and IgA in the bronchoalveolar lavage fluid (BALF) and serum of 61 adult patients with severe HIV infection and of 56 HIV− controls. Albumin was used as the serum transudation factor. The increase of immunoglobulin levels in the serum of HIV-infected patients was confirmed. The IgG level was also increased in epithelial lining fluid (ELF), whereas the total IgA level was unchanged and secretory IgA (SIgA) level was decreased. The ELF/serum immunoglobulin ratios suggested that the IgG present in ELF resulted mainly from transudation, in contrast to SIgA, which was synthesized locally in controls but greatly diminished in HIV-infected patients. IgG to HIV-1 could be detected in BALF of all the patients, but IgA to HIV-1 only in 30% of patients. BAL IgG reacted more consistently and with a broader array of HIV-1 antigens than did IgA. BAL IgA, when present in samples, reacted primarily with viral envelope antigens. Because IgA specificities to some HIV-1 antigens were detected more intensively by BAL than by serum immunoglobulins, we conclude that the mucosal immune response is distinct from that in serum. IgG antibody activity to Streptococcus pneumoniae was decreased in HIV-infected patients' sera, and IgA antibody activities to S. pneumoniae and to Pseudomonas aeruginosa were decreased in ELF in HIV-infected patients.
Infection with rat cytomegalovirus (CMV) in the immunocompromised host is associated with the appearance of a T cell population with reduced CD8 and T cell receptor (TCR) expression
Authors: VAN DAM J G , DAMOISEAUX J G M C , VAN DER HEIJDEN H A M D , GRAULS G , VAN BREDA VRIESMAN P J C , BRUGGEMAN C A 
Published: November 2003

SUMMARY
Infection with human cytomegalovirus (HCMV) mostly results in a chronic subclinical infection; the immune system is unable to eliminate the virus and is apparently in equilibrium with the persistent virus. In the immunosuppressed host this equilibrium is disturbed, resulting in clinical infection. Rat cytomegalovirus (RCMV) infection in its host can be used as a model for HCMV infection. Using flow cytometry we examined the effect of acute RCMV infection on the composition of leucocyte subsets in the peripheral blood of both immunocompetent and immunosuppressed (5 Gy total body irradiation) Lewis rats. Special attention was paid to the natural killer (NK) cells and the CD8+ T cells known to be involved in the control of viral infections. Furthermore, we determined the presence of leucocyte subsets in the internal organs by immunohistochemistry. In immunocompetent rats, infection caused a small increase in NK cells and a large increase in CD8+ T cells. In contrast, infection of immunosuppressed rats caused a marked increase in NK cells and a small increase in CD8+ T cells, consisting of T cells with reduced expression of both CD8 and TCR. This phenomenon is characteristic of anergic CD8+ T cells, possibly explaining the ability of the virus to escape elimination by the immune system. The increase of NK cells in the peripheral blood of immunosuppressed, RCMV-infected rats could also be detected in kidney, liver, lung and pancreas, but not in salivary gland. This could explain the long persistence of infectious virus in the salivary gland.
Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin κ light chain deposits. A human disease to study alterations of protein conformation
Authors: KAPLAN B , VIDAL R , KUMAR A , GHISO J , FRANGIONE B , GALLO G 
Published: November 2003

SUMMARY
Tissue deposition of monoclonal immunoglobulin light chains is a serious complication in some patients with B cell proliferative disorders. The deposits are typically fibrillar and Congophilic in amyloid (AL) and non-fibrillar and Congophobic in light chain deposition disease (LCDD), and rarely coexist in the same patient. From post-mortem tissue of an individual with fibrillar and non-fibrillar κ light chain deposits in different sites, we separately extracted and analysed biochemically and immunochemically the non-amyloid deposits from isolated glomeruli, the amyloid from isolated renal arteries and the amyloid from myocardium in which the only deposits were amyloid restricted to mural arteries. Western blotting analysis of both the extracted amyloid and the non-amyloid deposits demonstrated 25-kD bands immunoreactive with anti-κ antibody, and the identity of the N-terminal amino acid sequences that belong to the variable region κIV light chain subgroup. This is the first human disease in which antigenically similar but morphologically different deposits have been separately biochemically analysed. We propose that combined LCDD and AL is an ideal human disease to study the relationships and the factors that influence the conversion of non-amyloidogenic to amyloidogenic conformations.
Impaired Ca2+ mobilization by X-linked agammaglobulinaemia (XLA) B cells in response to ligation of the B cell receptor (BCR)
Authors: GENEVIER H C , CALLARD R E 
Published: November 2003

SUMMARY
XLA bone marrow samples were shown to contain B cells expressing IgM, and pre-B cells that express the μ-surrogate light chain (μψLC) complex, albeit at a reduced frequency to that found in normal bone marrow. Antibody ligation of μ heavy chain on these cells and an XLA B cell line did not induce a Ca2+ flux, whereas ligation of μ heavy chain on normal bone marrow cells, μψLC+ pre-B cell lines and an IgM+ B cell line did. The block in XLA B cells was not due to a defect in the basic mechanism of Ca2+ flux generation, as the cells responded well to thapsigargin. In addition, the defect did not affect T cells, which were shown to respond to CD3 antibody with a Ca2+ flux. Ligation of μ heavy chain on XLA bone marrow cells did, however, activate tyrosine kinases, resulting in tyrosine phosphorylation of a cellular protein with a molecular weight of approximately 115 kD. These results indicate that Btk may be necessary for the generation of the Ca2+ flux in response to ligation of μ heavy chain on B cells and μψLC+ pre-B.
T cell receptor (TCR) BV gene repertoires and clonal expansions of CD4 cells in patients with HIV infections
Authors: Roglic M , Macphee R D , Duncan S R , Sattler F R , Theofilopoulos A N 
Published: November 2003

Abstract
Despite extensive investigation, the pathogenesis of T cell depletions that characterize AIDS has not been elucidated. To study this process further, we evaluated T cell antigen receptor β-chain variable gene (TCRBV) repertoires in peripheral blood lymphocytes (PBL) of 23 HIV-infected patients. Expression levels of 28 TCRBV were determined by multiprobe RNase protection assay after polymerase chain reaction (PCR) amplifications. Abnormal expansions (&gt;2 s.d. from mean normal values) were frequent in HIV CD4, accounting for 26% of total measured TCRBV in this population. The number and magnitude of abnormalities among individuals were inversely proportional to their CD4 counts (P&lt;0.012 and P&lt;0.01, respectively). While abnormalities were not randomly distributed among TCRBV subfamilies, no particular genes were expanded or contracted among all patients. Only 14% of CD8 TCRBV were proportionally expanded (P&lt;0.01 compared with CD4), and there were limited concordances between paired CD8 and CD4 repertoires among individuals. CDR3 length analyses and TCRBV sequencing showed that most CD4 expansions comprised clonal or oligoclonal populations. Thus, T cell responses in HIV patients are characterized by severe TCRBV biases and clonal expansions among CD4 subsets, and these processes are exaggerated with disease progression. The heterogeneity and oligoclonality of the TCRBV expansions are consistent with responses to HIV-encoded or other conventional antigens rather than superantigenic effects. The presence of CD4 clonal proliferations in these patients may be important in the pathogenesis of HIV, and the absence or reduction of many T cell specificities due to oligoclonal expansions may increase susceptibility to opportunistic infections.
Febrile infection changes the expression of IgG Fc receptors and complement receptors in human neutrophils in vivo
Authors: Leino L , Sorvajärvi K , Katajisto J , Laine M , Lilius E-M , Pelliniemi T-T , Rajamäki A , Silvoniemi P , Nikoskelainen J 
Published: November 2003

Abstract
We have examined the expression of the IgG Fc receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3) in neutrophils from 42 patients with febrile bacterial infection, 20 patients with febrile viral infection and 69 non-febrile healthy individuals. Using receptor-specific MoAbs and immunofluorescence flow cytometry the relative fluorescence intensity (as a measure of receptor number) and the proportion of receptor-positive cells were determined in peripheral blood neutrophils exposed to minimal processing, consisting only of erythrolysis. Both the percentage of FcRI-positive neutrophils and FcRI number per neutrophil were significantly (P&lt;0.001 and P&lt;0.0001) increased in bacterial infected patients compared with controls, whereas in viral infected patients only the FcRI percentage was markedly elevated (P&lt;0.05). In addition, both FcRII and CR1 levels were significantly higher in the bacterial infection group than in the viral infection and control groups (bacterial versus control P&lt;0.001, bacterial versus viral P&lt;0.0001). No changes in expression of FcRIII or CR3 were found in the patient groups. The kinetic analysis of receptor expression in bacterial infection patients revealed a shift in the percentage of FcRI-bearing neutrophils towards normal values already on day 2 after the first analysis. On the other hand, the levels of FcRI, FcRII and CR1 remained clearly elevated in these patients during 1 week's follow-up period. We conclude that febrile infection may cause systemic activation of the entire pool of circulating neutrophils, resulting in alterations in cell surface receptor expression, some of which are characteristic of the nature of the infectious agent.
Growth hormone responses to growth hormone‐releasing hormone and clonidine in patients with type I diabetes and in normal controls: effect of age, body mass index and sex
Authors: Jacobs M. L. , Nathoe H. M. W. , Blankestijn P. J. , Stijnen Th. , Weber R. F. A. 
Published: November 2003

OBJECTIVE Increased plasma concentrations of GH and increased GH responses to provocative stimuli are reported in patients with poorly controlled type I diabetes and are suggested to be related to complications. Our aim was to investigate GH concentrations in moderately controlled patients.PATIENTS AND MEASUREMENTS We have investigated IGF‐I concentrations and fasting GH concentrations and the response to 1 μg/kg body weight GH‐releasing hormone (GHRH) intravenously and/or to 150 μg clonidine intravenously in 77 moderately controlled patients with type I diabetes and in 46 healthy controls.RESULTS Median HbA1c in the patients was 8.5% (upper level of normal 6.3%). Fasting GH and GH concentrations after the administration of GHRH were not significantly different in patients with type I diabetes compared with normal controls. Fasting and stimulated GH concentrations after the administration of clonidine were significantly higher in the patients, but this could be explained by their lower age and body mass index compared with controls. In controls but not in patients there was a negative correlation between GH and glucose concentrations. IGF‐I was significantly lower in patients with diabetes than in controls, even after correction for age, body mass index and sex.CONCLUSIONS Patients with moderately controlled type I diabetes mellitus have normal baseline and stimulated GH concentrations after the administration of GHRH or clonidine compared with healthy controls, when corrected for age, body mass index and sex. However, these ‘normal’ GH concentrations must be considered inappropriately high in view of the hyperglycaemia in these patients. The low plasma IGF‐I concentrations might be responsible for the GH over‐production.
The GnRH challenge test: a quantitative measure of pituitary desensitization during GnRH agonist administration
Authors: Scheele Fedde , Hompes Peter G. A. , Lambalk Cornelis B. , Schoute Erik , Broekmans Frank J. , Schoemaker Joop 
Published: November 2003

OBJECTIVE The use of GnRH agonists for desensitization of the pituitary is widespread in gynaecological practice. For indications such as contraception and treatment of uterine leiomyomata partial desensitization may suffice. With respect to partial desensitization of the pituitary we have addressed three basic questions: (1) Is the degree of pituitary desensitization dependent on the dose of agonist used? (2) What is the optimal way to measure the degree of pituitary desensitization? (3) Is it possible to create a standard to express the degree of pituitary desensitization?DESIGN AND PATIENTS Twenty‐four women were randomized into 4 groups of 6 women. To achieve pituitary desensitization, the groups received 0.1, 0.25, 0.5 and 1.0 μg/min GnRH respectively, for 6 weeks.MEASUREMENTS Pituitary desensitization was measured by gonadotrophin levels and responses to a 100‐μg bolus of GnRH and an oestradiol benzoate challenge‐test.RESULTS The level of LH and the responses of LH and FSH to the GnRH challenge showed significant dose‐dependent suppression. Multiple regression indicated the LH response to the GnRH challenge was the best way to measure pituitary desensitization. From the LH responses to the GnRH‐challenge a ‘standard curve’ was established for the assessment of the degree of pituitary desensitization.CONCLUSION The LH response to the GnRH challenge test is the best available measure of pituitary desensitization during GnRH agonist treatment.
Emission and content of monoterpenes in intact and wounded needles of the Mediterranean Pine, Pinus pinea
Authors: Loreto F. , Nascetti P. , Graverini A. , Mannozzi M. 
Published: November 2003

Abstract1. Biogenic emission of isoprenoids may be involved in protecting plants against pathogens and may interfere with the chemistry of atmosphere. Pinus pinea (L.) is one of the most widespread conifers in the Mediterranean area and is a potentially strong emitter of monoterpenes.2. We demonstrated by gas‐exchange studies that monoterpenes other than trans‐β‐ocimene are not emitted significantly by intact primary and secondary needles of 3‐year‐old P. pinea plants.3. Trans‐β‐ocimene emission is light‐ and CO2‐dependent. Therefore this compound is probably formed from photosynthetic carbon in the chloroplasts and does not originate from the same biochemical route as other monoterpenes stored in resin ducts.4. Trans‐β‐ocimene emission starts in spring, peaks in summer and ceases at the end of summer. This strong seasonality may mark a phase‐shift in needle ontogeny, but is not related strictly to changes in photosynthesis.5. Wounded needles, either illuminated or darkened, massively release monoterpenes contained in the ducts, primarily limonene and α‐pinene. Monoterpene release from wounded needles rapidly decreases but does not cease altogether, even after 24 h. The amount of monoterpenes emitted from wounded needles in 24 h can be estimated at about 1200 and 120 µmol g −1 day−1 (dry mass) of limonene and α‐pinene, respectively. Wounded needles are a main contributor to monoterpene emission by vegetation.6. Monoterpene content is two to three times greater in primary than in secondary needles. In primary needles, typical only of young plants, the elevated content of monoterpenes may allow plant survival against pathogenic attacks.
Diadenosine 5′,5′′′‐P1,P4‐tetraphosphate (Ap4A) controls the timing of cell division in Escherichia coli
Authors: Nishimura Akiko , Moriya Shigeki , Ukai Hideki , Nagai Kazuo , Wachi Masaaki , Yamada Yuko 
Published: November 2003

Background:The timing of the cell division in Escherichia coli is highly regulated, but its mechanism has not been identified. Previously we have found that the cfcA1 mutation uncouples DNA replication and cell division and elevates the frequency of cell division. We further analysed the structure and the role of the cfc genes of cfcA11, a derivative of cfcA1, and another cfc mutant, cfcB1.Results:The cfc mutants divided prior to the ordinary stage of cell division and produced many small cells with nucleoid. However, the cells grew exponentially, and the length of a cell cycle and the initiation mass for chromosome replication were not altered by the cfc mutations. These properties resulted from a reduction of the period between the nucleoid division and the cell division in a cell cycle, and a compensatory lengthening of the period between the cell division and the initiation of the next round of DNA replication. CfcA11 has a mutation in glySa which encodes the α‐subunit of glycyl‐tRNA synthetase, and cfcB1 has an IS2 insertion in apaH which encodes Ap4A hydrolase. The cfc properties of both cfc mutants were suppressed by a multicopy plasmid carrying apaH+, and the intracellular level of Ap4A in cfcA1 was 15‐fold higher, and cfcB1 was 100‐fold higher than their parent. Experiments using wild‐type cells showed that a high level of Ap4A caused early cell division, and that a low level of Ap4A caused delayed cell division.Conclusion:Ap4A is a signal for the induction of cell division. High levels of Ap4A are responsible for the initiation of cell division. The glyS mutation permits an efficient synthesis of Ap4A.
Sendai virus‐based expression of HIV‐1 gp120: reinforcement by the V(−) version
Authors: Yu Deshan , Shioda Tatsuo , Kato Atsushi , Hasan Mohammad K. , Sakai Yuko , Nagai Yoshiyuki 
Published: November 2003

Background:We have established a system for recovering Sendai virus (SeV), a nonsegmented negative strand RNA virus, entirely from cDNA at an extremely high rate, and have succeeded in creating a V(−) SeV whose gene expression was greatly enhanced by the deletion of the nonessential V gene. Because of its extreme medical importance, there has been a strong need for the establishment of a better system to express the gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV‐1) in sufficient quantity and purity. It also remains to be established to produce gp120 in in vitro natural host cells for HIV‐1 such as human primary blood mononuclear cells, macrophages or established T cell lines.Results:Using the above system, we created recombinant Sendai viruses expressing the gp120 in CV1 cells, a monkey kidney line. The expression level from the standard V(+) version has already reached 2.2 μg per 106 infected cells, which was readily purified from the culture fluid with a recovery rate of about 60%, and has so far appeared to be functionally and serologically authentic. The inserted gp120 gene was stably maintained during numerous passages of the recombinant virus. The V(−) version‐based expression was even more robust, consistently reaching over 6.0 μg per 106 cells, a level that is one of the highest currently attainable for gp120 production in mammalian cells. Furthermore, a broad host range of SeV allowed gp120 production in all the three natural host cells for HIV‐1 described above.Conclusions:SeV‐based expression serves as a novel choice for producing large quantities of HIV‐1 gp120 and will greatly facilitate biochemical, biological and immunological studies of this important glycoprotein.