bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data
Authors: Tsiara S. N. , Kapsali E. , Christou L. , Panteli A. , Pritsivelis N. , Bourantas K. L. 
Published: March 2003

Abstract: For elderly patients with multiple myeloma (MM), conventional melphalan and prednisone (MP) therapy has been the treatment of choice; the vincristine, doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who also receive high‐dose melphalan in combination with autologous or allogeneic bone marrow transplantation (BMT). Although survival time is similar in both the MP and VAD regimens, the continuous infusion of doxorubicin which the latter treatment entails constitutes a disadvantage along with the 4‐day hospitalization required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A modified form of VAD therapy includes liposomal doxorubicin (Caelyx®) (40 mg/kg for 1 d), oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more efficient and has fewer side effects than conventional doxorubicin, and it can be administered on an outpatient basis: dexamethasone can be given orally and vincristine in bolus infusion. In order to estimate its efficacy and tolerability, we administered this regimen to 12 patients (first‐line treatment in 6 patients, salvage therapy in 6 patients). All patients exhibited good tolerance to liposomal doxorubicin with no severe side effects. Eight patients achieved complete hematological remission and three partial response. One patient died before completing the treatment.In conclusion, compared to other therapies, this modified VAD regimen containing liposomal doxorubicin can be more easily administered to MM patients, without severe side effects and with increased full remission rates, almost similar to those with the conventional VAD treatment.
Epidermal CD8+ T cells in chronic plaque psoriasis are Tc1 cells producing heterogeneous levels of interferon‐gamma
Authors: Ovigne J.‐M. , Baker B. S. , Brown D. W. , Powles A. V. , Fry L. 
Published: March 2003

Abstract: The majority of epidermal CD8+ T cells in chronic plaque psoriasis are activated Tc1 cells producing interferon‐γ and no interleukin‐4, a small proportion of which express NK‐T receptors. To quantitate their level of cytokine production and characterize them further, CD8+T cells were isolated from epidermal cell suspensions of lesional biopsies from 24 patients with chronic plaque psoriasis. T‐cell lines (TCL) were established by culture of CD8+ T cells with feeders and IL‐2 for 11 days and expansion with PHA. Ten TCL were stained for surface markers; 6 were cloned with PHA by limiting dilution. Interferon‐γ, interleukin‐4 and interleukin‐10 production was measured by ELISA after PMA/anti‐CD3 activation of 15 TCL and 39 CD8+ T‐cell clones. The 10 TCL stained were CD8αβ+ (93.3%), T‐cell receptor‐αβ+ (99.5%), costimulatory molecule CD28+ (90.1%), with a small CD8αα+ population (2.3%). No NK‐T‐cell receptor CD158a or CD158b expression was detected, whilst CD94 was expressed on 6.2% of cells in 6/9 TCL. All the TCL and 37/39 CD8+ T‐cell clones produced interferon‐γ but no or minimal interleukin‐4 or interleukin‐10. The TCL produced a wide range of interferon‐γ levels (138 to 15,020 pg/ml). Clones from 3 patients showed low levels (60 to 1,410 pg/ml), from 2 patients high levels (6,105 to 43,040 pg/ml) and from 1 patient a wide range (405 to 36,010 pg/ml) of interferon‐γ production. Thus epidermal CD8+ Tc1 cells in chronic plaque psoriasis produce highly heterogeneous levels of interferon‐γ, which may reflect clinical diversity.
Is Stat3 activation in trophoblast cells required for invasiveness ?
Authors: Fitzgerald Justine S. , Corvinus Florian , Friedrich Karlheinz , Markert Udo R. 
Published: March 2003

OBJECTIVES:  Phosphorylation and dimerization of Stat3 (Signal Transducer and Activator of Tran‐ scription 3) is related to the malignancy of tumor cells and potentially to their invasive properties. Extravillous trophoblast cells resemble cancer cells in this aspect since they invade decidual tissue, although only up to a well‐regulated limit. We aim to investigate the contribution of Stat3 to this phenomenon.METHODS:  Extravillous trophoblast cells were isolated from human term placentae by mechanical and enzymatic tissue disaggregation, density gradient and magnet‐activated cell separation (MACS). Stat3 expression and tyrosine phosphorylation were studied by Western blot analysis, specific DNA‐binding activity of Stat3 was tested by an electrophoretic mobility shift assay (EMSA). For comparison, various tumor cells were investigated.RESULTS:  Trophoblast cells from term placentae express Stat3, which is inactive in native ex vivo cells. In contrast, cells from various invasive tumors display a high rate of activated Stat3. Currently, first trimester trophoblast and choriocarcinoma cells are studied in order to correlate their state of Stat3 expression/ activation with their degree of invasiveness.CONCLUSION:  The presence of Stat3 in trophoblast cells implicates its stimulatability, which might be related to their invasive phenotype. The lack of tyrosine phosphorylation of Stat3 in term tropho‐ blast cells might be due to their resting, non‐invasive status.
Cytokine profile in women with preeclampsia
Authors: Jonsson Yvonne , Ekerfelt Christina , Berg Göran , Ernerudh Jan , Nieminen Katri , Matthiesen Leif 
Published: March 2003

Preeclampsia is a severe complication engaging 5–10% of all pregnancies. Immune mechanisms have been suggested in the etiology of this disease.AIM:  To study the systemic spontaneous and fetus‐specific cytokine production by peripheral blood mononuclear cells (PBMCs) in women with preeclampsia and normal pregnancies.METHODS:  PBMCs from nine women with preeclampsia and five women with normal pregnancies were stimulated in mixed leukocyte cultures with paternal cells (representing the fetus) and autologous blood lymphocytes. The stimulated and spontaneous production of IL‐4, IL‐10 and IFN‐α were analysed by ELISPOT and IL‐12 and IL‐13 in cell‐culture supernatants by ELISA. Cell‐culture supernatants were collected for 2–7 days of incubation.RESULT:  The results are preliminary since analysis of data is going on. We found a trend of decreased IL‐10 production in response to paternal cells in preeclamptic women. Data for the other cytokines did not show any differences between groups.CONCLUSION:  The material studied so far is limited and further studies are needed to draw any safe conclusions.
Systemic cytokine response during listeria monocytogenes infection in pregnant BALB/C Mice
Authors: Abram Maja , Vuckovic Darinka , Doric Miljenko , Wraber Branka 
Published: March 2003

Pregnancy has an important impact on the maternal immune system, associated with a shift in the Th1/Th2 cytokine balance towards a type‐2 response. However, listeria induced Th1 type cytokines are essential in host protection against this facultative intracellular bacterium. We have analyzed and compared the kinetics of maternal serum concentrations of IFN‐γ, IL‐10, TNF‐α, IL‐6 and KC by ELISA. Serum IFN‐γ levels in infected pregnant mice were significantly reduced in comparison to infected virgin animals, while IL‐10 levels were increased, being significantly higher on days 3 and 6 p.i. as compared to infected virgin mice. Upon L. monocytogenes infection, circulating TNF‐α concentrations were below the detection limit. However, on day 6 p.i., in pregnant mice elevated levels of TNF‐α were noticed, correlating to the severity of disease. Increased concentrations of IL‐6 have been shown to follow the kinetics of bacterial numbers in the liver of infected animals. Murine chemokine KC production in maternal circulation followed a similar pattern as IL‐6.In comparison to virgin animals, pregnant mice mount lower levels of protective Th1 cytokines and are unable to eliminate the pathogen. Increased serum concentrations of IL‐10, along with proinflammatory cytokines, may well contribute to the severity of pregnancy‐associated listeriosis.Maternal serum IL‐6 level showed the highest correlation with the course of infection and pregnancy outcome.
Protective effect of Vitamin E in an animal model of LPS‐Induced inflammation
Authors: Iborra A. , Mayorga M. , Estany S. , Martínez P. 
Published: March 2003

Most sterility outcomes may be associated with the presence of an inflammatory response due to infections. This environment would lead to an inability of the endometrium to implant, protect and maintain viable embryos. We have established an animal model of inflammation in which the systemic administration of bacterial endotoxin (LPS) results in a low embryo implantation rate.OBJECTIVES:  To investigate the effect of the inflammatory agent LPS on the embryo viability. To verify the ability of vitamin E (VE) in preventing the effect of LPS.For preimplantation studies we used pregnant mice B6CBAF1 which were intraperitoneally (i.p.) inoculated with LPS alone or with liposomes containing different concentrations of VE 24 hr after LPS injection. The embryos were obtained from the oviduct and the preimplantation rate was evaluated.The treatment of pregnant female mice with LPS inoculated i.p. produces a decrease in the number of preimplantational embryos in a concentration dependent manner: as compared with non‐treated LPS mice (100%), we obtained a 50–35% of preimplantational embryos with LPS treated mice. This LPS effect can be partially reverted by the administration of VE in animals treated with 4 or 6 mg/kg of LPS, but not in 10 mg/kg LPS treated mice. Preliminary results show that inflammatory cytokines are secreted by i.p. macrophages in LPS treated mice. In the present work we demonstrate the ability of VE to avoid an inflammatory environment and to allow viability.
Expression of HLA‐G in the human placenta
Authors: Dohr G. , Blaschitz A. , Juch H. , Hutter H. 
Published: March 2003

The unique structure of the human placenta provides a separation between maternal and fetal tissues and circulations. Although the maternal–fetal proximity is very close, the placenta and the fetus are not rejected by the maternal immune system. Among the various factors implicated in the mother's tolerance of the fetus, a key factor has been attributed to HLA‐G molecules, which are expressed by specialized trophoblast cells. By the alternative splicing of its primary mRNA, HLA‐G, belonging to Class I MHC molecules, results in four membrane bound (HLA‐G1, ‐G2, ‐G3, ‐G4) and three soluble proteins (HLA‐G5, ‐G6, ‐G7). Which of these HLA‐G isoforms are expressed on the cell surface and which are secreted was the aim of our study.Whereas the generally agreed upon opinion is that the full length HLA‐G1 isoform is expressed by extravillous cytotrophoblast cells, the source of soluble HLA‐G5 isoform and the expression of all other isoforms in the human placenta is still under debate. However, soluble HLA‐G products, which might be present in body fluids, could also come from membrane bound HLA‐G1 by shedding; a process, that has been described for classical HLA molecules. HLA‐G expression in organs, other than placenta and certain tumors, has not yet been explained convincingly.Since immunological detection methods crucially depend on the antibodies and preparation techniques used, we investigated HLA‐G specific antibodies for their specificity and binding properties. We compared the binding ability of some antibodies on HLA‐G1, G2, ‐G5 transfected cell lines with naturally expressed placental HLA‐G molecules. A broad range of methods, from immunolocalization to protein‐biochemical and Elisa techniques, were used to clarify which HLA‐G isoform is actually expressed in the normal placenta.
The significance of women's natural killer cell receptors repertoire in the maintenance of pregnancy
Authors: Varla‐Leftherioti. Marighoula 
Published: March 2003

It has been suggested that decidual NK cells play a regulatory role in pregnancy with their heterocladic (activating/inhibitory) receptor repertoire to control trophoblast infiltration. Most of the NK receptors (NKRs) have as ligands HLA molecules (HLA‐C,‐G,‐E), which are expressed on invading trophoblast and they may interact with their NKR counterparts and provide self‐signals to evade trophoblastic damage.When we studied the NKR repertoire in couples with unexplained recurrent spontaneous abortions by genotyping partners for NKRs (KIR and CD94/NKG receptors, known to have as ligands HLA molecules present on trophoblast), we found that aborting women usually have a limited inhibitory KIR (inhKIR) repertoire.Our hypothesis that a limited inhKIR repertoire predisposes to miscarriage, because it is ineffective to abort activating signals and protect trophoblast, is supported by studies in selected couples, known to posses HLA‐Cw antigens interacting with inhKIRs and by studies on the placental material of spontaneously lost or electively terminated pregnancies. Most of the aborters did not have inhKIRs specific for the HLA‐C antigens possibly expressed on trophoblast and this seems to be confirmed when KIRs and HLA‐Cs are genotyped using DNA extracted from decidual and trophoblastic cells, respectively.Increasing knowledge about KIR haplotypes is expected to be helpful in the study of the suggestedinhKIR – HLA‐C allorecognition system in pregnancy.
Effects of Cytokines on VEGF Expression and Secretion by Human First Trimester Trophoblast Cell Line
Authors: CHOI SUN JU , PARK JOO YOUNG , LEE YOUNG KYU , CHOI HYUN IL , LEE YOUNG SIM , KOH CHOON‐MYUNG , CHUNG IN‐BAI 
Published: March 2003

PROBLEM: The mechanism through which vascular endothelial growth factor (VEGF) regulation occurs at the feto‐maternal interface is poorly understood. The aim of this study was to investigate the effects of various cytokines on VEGF expression and secretion by trophoblast cells.METHOD OF STUDY: We investigated the effects of cytokines on VEGF expression in human first trimester trophoblast cell line by analyzing VEGF messenger RNA (mRNA) by reverse transcription‐polymerase chain reaction and VEGF protein secretion by enzyme linked immunosorbent assay.RESULTS: The trophoblast cells expressed VEGF mRNA constitutively and the main subtypes were identified as VEGF121 and VEGF165. When cultured in the presence of interferon (IFN)‐γ, interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐2, or IL‐10, VEGF mRNA expression was found to be significantly increased by IL‐1β, IFN‐γ and TNF‐α but to be unaffected by IL‐2 and IL‐10. Moreover, VEGF secretion was most significantly increased by IFN‐γ treatment.CONCLUSION: These results suggest that IL‐1β, IFN‐γ, and TNF‐α may regulate the production of VEGF in early gestational trophoblasts.
Collagenase‐3 (MMP‐13) in Fetal Membranes and Amniotic Fluid During Pregnancy*
Authors: Fortunato Stephen J. , LaFleur Bonnie , Menon Ramkumar 
Published: March 2003

OBJECTIVE:  To examine the expression, site of production and a role of collagenase‐3 in human fetal membranes and amniotic fluid (AF).METHODS:  Amniochorion collected at the time of elective repeat cesareans prior to labor from normal term gestation, were placed in an organ explant system for 72 hr. The AF was collected from the following groups of women: women at term; women at third trimester pregnancy: women at mid‐trimester pregnancy. Women with premature rupture of the membranes (PROM) with or without pre‐term labor and infection delivered by cesareans before term; women with pre‐term labor and no rupture of membranes and delivered by cesareans before term; The mRNA expression of collagenase‐3 was studied by reverse transcriptase–polymerase chain reaction (RT–PCR) and protein concentrations in the AF were assayed by enzyme‐linked immunosorbent assay (ELISA). Site of collagenase‐3 production was documented by immunohistochemistry. Statistical comparisons were made using ANOVA. All statistical hypotheses were adjusted for multiple comparisons using the Scheffe method of adjustment.RESULTS:  Amniochorion at term expressed collagenase‐3 mRNA. Immunohistochemistry localized collagenase‐3 in both amnion and chorion. Collagenase‐3 was seen in AF from all gestational age groups with lowest levels at mid‐trimester [167.8 pg/mL] and highest during term labor (323.92 pg/mL) with no statistically significant difference between term and third trimester (310.11 pg/mL). AF levels of collagenase‐3 were significantly higher in women with pre‐term labor (370.02 pg/mL; Padj = 0.046) or pre‐term labor and infection (628.73 pg/mL; Padj = 0.002) compared with PROM with pre‐term labor and infection (87.19 pg/mL).CONCLUSION:  Collagenase‐3 mRNA is constitutively expressed and produced in amniochorion. It is a normal physiologic constituent of AF. PROM is not associated with an increase in the AF collagenase‐3.
Pre‐ovulatory Granulosa Cells of Infertile Women with Endometriosis are Less Sensitive to Luteinizing Hormone
Authors: Cahill David J. , Harlow Christopher R. , Wardle Peter G. 
Published: March 2003

Cahill DJ, Harlow CR, Wardle PG. Pre‐ovulatory granulosa cells of infertile women with endometriosis are less sensitive to luteinizing hormone. AJRI 2003; 49:66–69 © Blackwell Munksgaard, 2003PROBLEM:  Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic–pituitary–ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis.METHOD OF STUDY:  Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls.RESULTS:  Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58–9.24) versus 0.33 (0.28–0.72) ng/mL, P=0.019], indicating reduced sensitivity to LH.CONCLUSIONS:  In women with endometriosis, granulosa cells were less sensitive to LH stimulation. This provides further evidence for primary ovarian dysfunction as a significant contributory cause of the associated subfertility.
The effects of β2 adrenoceptor gene polymorphisms  on pressor response during laryngoscopy and tracheal intubation
Authors: Kim N.‐S. , Lee I.‐O. , Lee M.‐K. , Lim S.‐H. , Choi Y.‐S. , Kong M.‐H. 
Published: March 2003

SummaryWe investigated whether human β2 adrenoceptor (β2AR) gene polymorphisms are associated with the pressor response to laryngoscopy and tracheal intubation. Ninety‐two patients undergoing elective surgery under general anaesthesia were enrolled into this study. Arterial systolic pressure, heart rate and rate pressure product were measured before induction of anaesthesia and 1 min following laryngoscopy and tracheal intubation. Genomic DNA was then used to identify the β2AR‐16 and β2AR‐27 genes using an allele‐specific polymerase chain reaction method. Using multiple linear regression models, controlling for age, sex, weight, baseline blood pressure, heart rate and rate pressure product, we found that patients who possessed the glutamic acid homozygote of β2AR‐27 produced significantly greater changes in mean arterial pressure and rate pressure products than patients with the glutamine homozygote of β2AR‐27 (β coefficient for mean blood pressure = 11.81, β coefficient for pulse−pressure product = 8.76, both p‐values = 0.023). These findings suggest that genetic variability in the human β2AR gene polymorphisms may be associated with the pressor response to laryngoscopy and tracheal intubation.
Tracheal trauma from percutaneous tracheostomy  using the Griggs method
Authors: Watters M. , Thorne G. , Cox C. , Monk C. 
Published: March 2003

SummaryIn a safety evaluation study, relative force and distance measurements during percutaneous tracheostomy were recorded using specially monitored Griggs guidewire dilating tracheostomy forceps on 12 cadavers scheduled to undergo postmortem examination the same day. All measurements were recorded in millivolts and were converted to force and distance via appropriate calibration tables. Markedly more force was required for tracheal destruction than for therapeutic tracheal dilation (87.7 N ± 19 N vs. 31.6 N ± 17.1 N, p < 0.001). Also relatively less force was required for therapeutic tracheal dilation than for dilation of the pretracheal tissues␣(44.4 N ± 17.1␣N vs. 31.6 N ± 17.1 N, p < 0.05). These results suggest that the Griggs tracheostomy forceps have a reasonable margin of safety in that tracheal destruction is unlikely to occur inadvertently during therapeutic dilation. Second, the dilation of pretracheal tissues can act as useful guide in knowing how much force to apply in a therapeutic dilation.
Evaluation of the clinical usefulness of isolation of fetal DNA from the maternal circulation
Authors: Siva Sashi C. , Johnson Sylvia I. , Mccracken Sharon A. , Morris Jonathan M. 
Published: March 2003

AbstractObjective: To assess the reliability of isolating free fetal DNA from maternal plasma and to evaluate its clinical usefulness.Design: Fetal DNA was isolated from plasma or serum that was either collected prospectively or from archived samples collected for the purposes of second trimester screening.Methods: Prospective samples were collected from patients undergoing prenatal diagnostic procedures (n = 24). A second group of samples from Rhesus negative women (n = 28) were assayed in which blood had originally been collected for maternal triple serum screening. DNA was extracted from all samples and assayed for the presence of the β‐globin gene, sex‐determing region Y (SRY) gene and Rh gene. All DNA sample handling and extraction was carried out by a single operator, and polymerase chain reaction (PCR) was carried out using previously published PCR primers and appropriate controls. The accuracy of results was assessed relative to the karyotype in the case of the SRY gene or cord blood phenotype in the case of the Rh gene.Results: The SRY PCR results were compared to fetal cell karyotypes obtained from invasive diagnostic testing, 21 out of the 24 samples were correctly ‘sexed’. The RhD PCR results were compared to fetal cord blood samples at the time of delivery, and showed both false positive and false negative results. Two RhD negative babies were genotyped as RhD positive, despite repeat analysis.Conclusion: It is possible to isolate fetal DNA from maternal serum. It is a potentially clinically useful technique in our laboratory and can be used to detect male fetuses, and Rh negative fetuses. To be useful in clinical practice, it is necessary to safeguard against contamination at the time of sample handling, and to use the optimal range of primers available to cover the polymorphisms present within the RhD gene. Although not robust enough yet to be used with diagnostic certainty in our hands, immense improvements in technique, probes and real‐time PCR equipment make this type of diagnosis a reality in the near future.