bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser resurfacing of the skin for the improvement of facial acne scarring: a systematic review of the evidence
Authors: Jordan R. , Cummins C. , Burls A. 
Published: March 2003

Abstract
This review presents and evaluates the evidence of the effectiveness of laser resurfacing for facial acne scars. Primary studies of all types of design in any language were identified from MEDLINE, EMBASE, the Cochrane database, Science Citation Index and various internet sites. Studies were accepted if they included patients treated by any laser for atrophic or ice-pick acne scars. The quality of the studies was assessed and data extracted by two independent researchers. There were no controlled trials but 14 case series were found which reported the effects of either the carbon dioxide or erbium:YAG laser. All of the studies were of poor quality. The types and severity of scarring were poorly described and there was no standard scale used to measure scar improvement. There was no reliable or validated measure of patient satisfaction; most improvement was based on visual clinical judgement, in many cases without blinded assessment. The inaccurate use of ordinal scales meant that any improvement was impossible to quantify with any validity, although the evidence suggested that laser treatment had some efficacy (a range in individual patients of 25–90% for both the carbon dioxide laser and the erbium:YAG laser). Changes in pigmentation as a side-effect were common (in up to 44% of patients), although lasting only a few weeks. Laser resurfacing technology is increasingly used in clinical practice to treat acne scars. Despite the poor quality evidence, it is plausible that there is some improvement of acne scarring; there is insufficient information, however, for patients to make informed decisions on whether to opt for treatment and there is not enough evidence to compare the two types of laser. There is a particular lack of information about the psychological effects of acne scar improvement. Good quality randomized controlled trials are needed with standardized scarring scales and validated patient outcome measures in order to assess the effectiveness of laser resurfacing in this group of patients.
Expression of the inducible isoform of nitric oxide synthase in pigment cell lesions of the skin
Authors: Ahmed B. , Van Den Oord J.J. 
Published: March 2003

Abstract
Nitric oxide (NO) is a small molecule produced during the conversion of l-arginine to l-citrulline by NO synthase (NOS). Several isoforms of NOS exist, of which the Ca2+-independent, inducible NOS (iNOS or NOS2) is most prominently expressed by macrophages. iNOS activity and increased levels of iNOS have been found in various tumours and tumour cell lines but not in normal tissues; however, the precise role of NO in tumour progression has yet to be elucidated. We studied the expression of iNOS in paraffin sections of 41 benign naevi and 52 primary malignant melanomas (MM) of the skin, as well as in 13 metastatic MM. In addition, nitrotyrosine, indicative of NO production and formation of peroxynitrite, was studied in frozen sections of 13 naevi and 30 MM. Virtually all naevi expressed iNOS, but very few expressed nitrotyrosine, indicating either that iNOS in naevi is functionally inactive, or that naevus cells lack reactive oxygen radicals and thus do not form peroxynitrite. Normal melanocytes in adjacent uninvolved skin were unreactive for both markers. In MM, iNOS was most frequently expressed in the ‘pure’ and ‘invasive’ radial growth phase (RGP), whereas expression in the vertical growth phase (VGP) and metastatic phase occurred only in 76% of cases; moreover, in these latest phases of tumour progression, iNOS staining was weak and focal. We conclude that iNOS is expressed de novo in most benign pigment cell lesions. In MM (iNOS-generated) NO appears to play an important part in the early steps of invasion (i.e. the ‘invasive’ RGP), where it may stimulate neo-angiogenesis and may be a prerequisite for further tumour progression; this view is also supported by the finding of iNOS in the associated blood vessels in the papillary dermis. Finally, our data suggest that (iNOS-generated) NO plays a less significant part in the VGP and in metastatic melanoma.
Linear IgA disease with IgA antibodies directed against 200- and 280-kDa epidermal antigens
Authors: Fujimoto W. , Ohtsu T. , Toi Y. , Nakanishi G. , Arata J. 
Published: March 2003

Abstract
We report an 80-year-old man with the lamina lucida type of linear IgA disease, with IgA autoantibodies reactive with 200-kDa and 280-kDa epidermal proteins. The patient presented with widespread bullous lesions on his trunk and extremities without mucosal involvement. Histopathology of lesional skin showed a subepidermal blister with papillary microabscesses of neutrophils and a few eosinophils. Direct immunofluorescence microscopy of perilesional skin showed linear deposits of IgA and C3 at the basement membrane zone. The patient’s serum contained IgA autoantibodies that bound exclusively to the epidermal side of 1 mol L−1 NaCl split skin as determined by indirect immunofluorescence microscopy. Circulating IgA autoantibodies to 200- and 280-kDa antigens were detected in the patient’s serum by immunoblot analysis using extracts from normal human epidermis and human epidermal keratinocytes. These two antibodies, eluted from individual nitrocellulose membranes, reacted with the epidermal side of 1 mol L−1 NaCl split skin on indirect immunofluorescence microscopy, and bound to hemidesmosomes as determined by immunoperoxidase electron microscopy. This observation suggests the presence of hitherto uncharacterized 200- and 280-kDa hemidesmosomal proteins distinct from BPAG1, BPAG2 and β4 integrin as target antigens in linear IgA disease.
Direct activation of factor X by monocytes occurs during cardiopulmonary bypass
Authors: Parratt Rachel , Hunt Beverley J. 
Published: March 2003

We hypothesized that monocyte procoagulant activity, which includes up‐regulation of tissue factor and direct activation of factor X by CD11b, is an activator of coagulation during cardiopulmonary bypass (CPB), because recent studies have cast doubt on the presumption that the surfaces of CPB activate the intrinsic pathway.Sequential samples were taken from 17 patients undergoing cardiac surgery. During CPB a significant increase in thrombin–antithrombin complexes occurred (P<0.0005). Factor XIIa levels increased (P<0.005) but remained within the normal range. Total monocyte procoagulant activity was measured and a functional assay was developed to detect direct activation of factor X alone. There was a significant increase in total procoagulant activity on circulating monocytes from the start of CPB (P<0.005) to which direct factor X activation was a major contributor (P<0.05). Direct activation of factor X was inhibited by CD11b blocking peptides. Using flow cytometry, up‐regulation of monocyte CD11b (P<0.0005), but not up‐regulation of tissue factor, was found on circulating monocytes. Monocytes adherent on the oxygenator fibres showed increased CD11b expression (P<0.0001), but no tissue factor when assessed by fluorescent image analysis.In conclusion, direct activation of factor X through monocyte CD11b occurs during CPB and appears to contribute to thrombin generation during CPB.
Nodal T‐cell lymphoma in an HTLV‐I‐endemic area: proviral HTLV‐I DNA, histological classification and clinical evaluation
Authors: Ohshima Koichi , Suzumiya Junji , Sato Kensaku , Kanda Motonobu , Sugihara Midori , Haraoka Seiji , Takeshita Morishige , Kikuchi Masahiro 
Published: March 2003

Adult T‐cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T‐cell leukaemia virus type I (HTLV‐I). The histology usually indicates a pleomorphic type, but is not consistent. To clarify the relationship between the histological classification and prognosis in ATLL, and to confirm the significance of clonal HTLV‐I integration, we reclassified 572 cases with nodal T‐cell lymphoma in which the T‐cell phenotype and/or genotype was confirmed. In all cases the clonal integration of HTLV‐I proviral DNA in the lymph nodes was examined by Southern blot analysis. In addition, anti‐ATL antigen (ATLA) determination in the serum or PCR analysis of HTLV‐I pX amplification in lymph nodes was also performed. 66/313 (21%) cases with ATLA had no evidence of clonal HTLV‐I integration. 572 cases were classified into three groups: (A) cases with clonal integration (247 cases), (B) cases with ATLA without clonal integration of HTLV‐I proviral DNA (66 cases), (C) cases without ATLA (259 cases). Histologically, groups B and C frequently demonstrated large cell type and angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) type; however, group A tended to show a pleomorphic type. Clinically, group A showed a poorer prognosis than groups B and C.In conclusion, group A cases were defined as ATLL (HTLV‐I‐associated T‐cell lymphoma), whereas group B was classified as T‐cell lymphoma, which had coincidently occurred in HTLV‐I infected carriers. The simplified classification of REAL indicated clinical outcome: the prognosis of ATLL was poor, the unspecified type was intermediate, whereas the other types of lymphoblastic, AILD and anaplastic large cell type were all relatively favourable.
Cell lineage specific involvement in acute promyelocytic leukaemia (APL) using a combination of May‐Grünwald‐Giemsa staining and fluorescence in situ hybridization techniques for the detection of the translocation t(15;17)(q22;q12)
Authors: Haferlach Torsten , Löffler Helmut , Nickenig Christina , Ramm‐Petersen Lotte , Meeder Marlies , Schoch Robert , Schlegelberger Brigitte , Schnittger Susanne , Schoch Claudia , Hiddemann Wolfgang 
Published: March 2003

Acute promyelocytic leukaemia (APL) is strongly associated with the translocation t(15;17) which therefore provides a reliable marker to assess the potential involvement of different cell lineages. Six cases with morphologically, cytogenetically and molecularly proven APL were analysed at diagnosis or relapse by combining fluorescence in situ hybridization (FISH) with standard May‐Grünwald‐Giemsa (MGG) staining at the single cell level on bone marrow and blood smears. With the FICTION technique, combining immunophenotyping with FISH, haemopoietic precursor cells were identified using monoclonal antibodies against CD34, B‐ and T‐lymphocytes could be identified with CD19 and CD3. In addition, HLA‐DR‐positive cells were studied for the presence of t(15;17).Morphologically identified myeloblasts were relocated on the smear after FISH and were found to be PML/RARA positive in 91%, abnormal promyelocytes in 97%. In contrast, a positive signal was obtained in only 18% of PMN. Erythroblasts, lymphocytes and plasma cells did not show a PML/RARA rearrangement. Accordingly, all cells expressing CD3 or CD19 were PML/RARA negative. CD34 positive precursor cells identified by FICTION were PML/RARA positive in 97%. HLA‐DR‐positive cells contained a PML/RARA rearrangement in 24% of cells in one case and were negative in the two other cases investigated. These data indicate that APL appears to originate from a level of haemopoietic precursor cells but is restricted to the myeloid lineage. The low proportion of PML/RARA‐positive PMN points to the impairment of blast cell differentiation beyond the promyelocyte stage but also emphasizes the existence of normal residual haemopoietic stem cells from which PML/RARA‐negative PMN must be derived.
Tumour lysis syndrome complicating high‐dose treatment in patients with multiple myeloma
Authors: Fassas Athanasios B.‐T. , Desikan K. R. , Siegel David , Golper Thomas A. , Munshi Nikhil C. , Barlogie Bart , Tricot Guido 
Published: March 2003

Tumour lysis syndrome (TLS), because of its low proliferative activity, is thought to only rarely complicate the treatment of patients with multiple myeloma. However, as more aggressive therapeutic approaches are increasingly used in the management of this disease, it is conceivable that clinicians will encounter this complication more frequently.A retrospective analysis of > 800 patients with multiple myeloma treated at the University of Arkansas identified nine patients who developed a marked tumour lysis syndrome following intermediate‐ or high‐dose chemotherapy. Evaluation of disease characteristics revealed association with high tumour mass, high proliferative activity, increased lactic dehydrogenase levels, plasmablastic morphology, and unfavourable cytogenetic abnormalities.Recognition of multiple myeloma patients at high risk for the development of tumour lysis syndrome and prompt intervention are required especially in the presence of abnormal baseline renal function frequently complicating the clinical course of these patients.
High levels of lung resistance related protein mRNA in leukaemic cells from patients with acute myelogenous leukaemia are associated with inferior response to chemotherapy and prior treatment with mitoxantrone
Authors: Xu Dawei , Areström Irène , Virtala Robert , Pisa Pavel , Peterson Curt , Gruber Astrid 
Published: March 2003

Expression of the mdr1 (multidrug resistance), mrp (multidrug resistance associated protein), and lrp (lung resistance related protein) genes is associated with transport related MDR (multidrug resistance). We quantified mRNA levels of these genes using competitive reverse transcription polymerase chain reaction (RT‐PCR) in 128 samples of leukaemic cells from 92 patients with acute myelogenous leukaemia (AML).There was a wide variation between the samples in mRNA levels of all three genes. The mean mdr1 mRNA level was 1.3 transcripts per cell (range undetectable to 15.8), the mean mrp level was 7.9 (range 0.1–36.2) and mean lrp 3.9 (range 0.1–29).Lrp mRNA levels were higher in samples drawn at diagnosis from the 15 patients with resistant disease than from the 37 with chemosensitive disease (4.9 SD 3.1 v 2.9 SD 2.3, P = 0.016). Neither mdr1 nor mrp mRNA levels were predictive for response to chemotherapy. In samples from patients who had received chemotherapy, those that had received mitoxantrone (n = 24) had higher lrp mRNA levels (mean 4.8, SD 2.5) than those that had not (n = 20, mean 2.8, SD 2.4, P = 0.012).In conclusion, the results indicate that lrp expression is associated with inferior response to chemotherapy in AML and that lrp expression increases after exposure to mitoxantrone.
The effect of p53 dysfunction on purine analogue cytotoxicity in chronic lymphocytic leukaemia
Authors: Pettitt  , Sherrington  , Cawley  
Published: March 2003

To clarify the role of p53 in the killing of chronic lymphocytic leukaemia (CLL) cells by purine analogues, we examined the cytotoxic effects of chlorodeoxyadenosine and fludarabine on CLL cells that had been characterized according to their p53 functional status.Cases of CLL with p53 dysfunction (n = 7) displayed slight, but significant, resistance to nucleoside‐induced cell killing when compared with cases with functionally intact p53 (n = 12). The small difference between the two groups indicated that p53 plays a minor role in such killing.These findings suggest that the poor therapeutic response to purine analogues observed in patients with p53 defects is likely to be caused by the emergence, on a background of genomic instability, of CLL‐cell clones that are resistant to nucleoside‐induced killing for reasons unrelated to p53.
Circulating clonal cells in multiple myeloma do not express CD34 mRNA, as measured by single‐cell and real‐time RT‐PCR assays
Authors: Rasmussen Thomas , Jensen Linda , Honoré Lone , Andersen Heidi , Johnsen Hans Erik 
Published: March 2003

The peripheral blood (PB) mononuclear cells in patients with multiple myeloma (MM) have been reported to include CD34‐expressing cells that are clonally related to the myeloma cells. To determine whether there were elevated levels of CD34 mRNA or whether CD34+ cells in the PB include myeloma‐related cells, we developed a quantitative real‐time and a competitive CD34 RT‐PCR assay working on single flow‐sorted cells. Myeloma‐specific cells were detected with allele‐specific oligonucleotides (ASO) IgH PCR. PBSC products and mononuclear cell fractions in blood from normal donors, untreated and treated myeloma patients were analysed.When measured by flow cytometry, the numbers of CD34+/CD19+ cells were consistently < 0.1% of the mononuclear cells. In addition, no significant difference was found in the levels of CD34 mRNA between normal subjects and untreated MM patients (P = 0.935). In the treated group of MM patients the CD34 mRNA levels were significantly reduced (P = 0.052) because of the stem cell toxicity of melphalan. Further, no cells clonally related to the MM clone were found within the CD34 compartment, defined by a sort‐gate that included all cells expressing CD34 mRNA, as no cells outside the used CD34 sort‐gate had a detectable level of CD34 mRNA. We conclude that in myeloma patients, the myeloma clone is not found within the CD34 compartment.
Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases
Authors: Hellström Lindberg Eva , Schmidt‐Mende Jan , Forsblom Ann Mari , Christensson Birger , Fadeel Bengt , Zhivotovsky Boris 
Published: March 2003

Treatment with granulocyte colony‐stimulating factor plus erythropoietin may improve haemoglobin levels in patients with ringsideroblastic anaemia (RARS) and reduce bone marrow apoptosis. We studied bone marrow from 10 RARS patients, two of whom were also investigated after successful treatment. Mononuclear, erythroid and CD34+ cells were analysed with regard to proliferation, apoptosis, clonogenic capacity and oncoprotein expression, in the presence or absence of Fas‐agonist, Fas‐blocking antibody 2 and caspase‐3 inhibitor. During culture, RARS bone marrow cells showed higher spontaneous apoptosis (P < 0·05) and caspase activity (P < 0·05)) than bone marrow cells from healthy donors. Eight out of nine patients had reduced growth of erythroid colony‐forming units (CFU‐E) (< 10% of control) and granulocyte–macrophage CFU (CFU‐GM) (< 50% of control) from CD34+ cells. Fas ligation increased apoptosis and decreased colony growth equally in RARS and controls, but caused significantly more caspase activation in RARS (P < 0·01). Fas‐blocking antibody showed no significant inhibitory effect on spontaneous apoptosis or ineffective haematopoiesis, as measured using phosphatidylserine exposure, the terminal deoxynucleotide transferase‐mediated dUTP‐biotin nick‐end labelling technique, caspase activity or clonogenic growth. Caspase inhibition reduced apoptosis, increased proliferation and enhanced erythroid colony growth from CD34+ cells in RARS, but showed no effect on normal cells. CFU‐E improved > 1000% after successful treatment. Thus, erythroid apoptosis in RARS is initiated at the CD34+ level and growth factor treatment may improve stem cell function. Enhanced caspase activation at the stem cell level, albeit not mediated through endogenous activation of the Fas receptor, contributes to the erythroid apoptosis in RARS.
Complexes of anti‐prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces
Authors: Simmelink Marleen J. A. , Horbach Daniëlle A. , Derksen Ronald H. W. M. , Meijers Joost C. M. , Bevers Edouard M. , Willems George M. , De Groot Philip G. 
Published: March 2003

We investigated the mechanism by which anti‐prothrombin antibodies cause lupus anticoagulant (LAC) activity. Addition of affinity‐purified anti‐prothrombin antibodies from LAC‐positive plasma samples (α‐FII‐LAC+) to normal plasma induced LAC activity. Upon increasing the phospholipid concentration, LAC activity was neutralized. Addition of purified α‐FII‐LAC+ to normal plasma strongly inhibited factor Xa formation. No inhibition was measured when α‐FII‐LAC+ were added to prothrombin‐deficient plasma or when purified anti‐prothrombin antibodies from LAC‐negative plasma samples (α‐FII‐LAC−) were added. When a combination of prothrombin and α‐FII‐LAC+ was added to the purified clotting complex, a strong inhibition of factor Xa and IIa formation was seen. The α‐FII‐LAC+ alone or a combination of prothrombin and α‐FII‐LAC− did not show inhibition. Ellipsometry studies showed that, in the presence of α‐FII‐LAC+, the affinity of prothrombin for a phospholipid surface increased dramatically, whereas a much lower increase was observed with α‐FII‐LAC−. Our results show that complexes of prothrombin and anti‐prothrombin antibodies with LAC activity inhibit both prothrombinase and tenase. The antibodies increase the affinity of prothrombin for the phospholipid surface, thereby competing with clotting factors for the available catalytic phospholipid surface, a mechanism similar to that of anti‐β2‐glycoprotein I antibodies.
Red cell antibodies in patients with homozygous sickle cell disease: a comparison of patients in Jamaica and the United Kingdom
Authors: Olujohungbe Ade , Hambleton Ian , Stephens Lorna , Serjeant Beryl , Serjeant Graham 
Published: March 2003

The transfusion history and frequency of red cell antibodies in patients with homozygous sickle cell (SS) disease have been compared in 190 subjects from the Jamaican cohort study and 37 patients attending a sickle cell clinic in Manchester, England. The proportion of patients transfused did not differ between the groups although the number of units transfused and the frequency of red cell antibodies were significantly greater in the Manchester group. Immune antibodies occurred in three Jamaicans (2·6% of those transfused) and 16 UK subjects (76% of those transfused). Multiple antibodies occurred in 10 (63%) UK subjects but in no Jamaicans. Indications for transfusion also differed between the groups, Jamaican patients typically receiving 1–2 units for acute anaemia or acute chest syndrome, whereas UK patients frequently had multiple transfusions in preoperative exchange or prophylaxis programmes. The greater red cell alloimmunization among UK patients probably reflects both the greater use of transfusion and the disparity between donor and recipient populations in the UK.
Intracellular Fas ligand is elevated in T lymphocytes in severe aplastic anaemia
Authors: Luther‐Wyrsch Annette , Nissen Catherine , Wodnar‐Filipowicz Aleksandra 
Published: March 2003

Increased expression of Fas receptor by haemopoietic progenitors in aplastic anaemia (AA) suggests that excessive apoptosis contributes to multilineage bone marrow (BM) failure. To investigate the role of Fas ligand (FasL) in triggering progenitor cell death, we examined FasL levels in T lymphocytes of patients with severe untreated AA (n = 8). Expression of FasL on the surface of CD3+cells was not detectable. However, flow cytometric analysis of saponin‐permeabilized cells demonstrated higher levels of intracellular FasL in AA than in normal T cells (P < 0·005), both prior to and following activation with phytohaemagglutinin. Confocal microscopy revealed that FasL‐specific signals overlapped with cathepsin D staining, indicating that intracellular FasL is stored in lysosomal granules. Levels of intracellular FasL in patients examined 1 month after immunosuppression with antilymphocyte globulin and cyclosporin A were lower than prior to treatment. The caspase inhibitors, DEVD and zVAD, enhanced colony formation and prolonged survival of AA BM cells in liquid cultures by about 10‐fold (P < 0·05). Taken together, these data provide further evidence that apoptosis by the Fas/FasL system plays a role in the depletion of stem cells in AA.