bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX
Authors: Krackhardt Angela M. , Witzens Mathias , Harig Sabine , Hodi F. Stephen , Zauls A. Jason , Chessia Morgan , Barrett Patrick , Gribben John G. 
Published: August 2002

AbstractChronic lymphocytic leukemia (CLL) is associated with a variety of immunologic disturbances. Hypogammaglobulinemia and autoimmune phenomena are both often present in this disease. In contrast, humoral or cellular antitumor responses are rarely observed. It has been previously shown that antigens detected in patients with malignant diseases can provide information regarding intracellular molecules engaged in the transformation process and can identify tumor antigens that may be useful for development of immunotherapeutic strategies. Serologic identification by recombinant expression cloning (SEREX) has been demonstrated to be a useful method to detect tumor and tumor-associated antigens in a variety of malignancies. Although this approach is complicated in CLL, we used a modified SEREX approach and identified 14 antigens (KW-1 to KW-14) using this methodology. Several clones showed a restricted expression pattern in normal tissues. Moreover, distinctive expression of splice variants and aberrant gene expression in malignant tissue were detected. In this study, 6 antigens were detected exclusively in patients with CLL. Eight antigens were detected also in lymphoma patients. Healthy donors showed antibody responses against only 3 of the identified antigens. T cells with specific cytotoxicity against peptides derived from the 2 antigens tested could be generated from healthy donors. These findings demonstrate that humoral and cellular immune responses against CLL-associated antigens can be detected. Ongoing experiments investigate their potential for the development of immunotherapeutic strategies.
Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations
Authors: Bosio Sandra , De Gobbi Marco , Roetto Antonella , Zecchina Gabriella , Leonardo Eugenio , Rizzetto Mario , Lucetti Claudio , Petrozzi Lucia , Bonuccelli Ubaldo , Camaschella Clara 
Published: August 2002

AbstractAceruloplasminemia is a recessive disorder characterized by anemia, iron overload, and neurodegeneration, caused by the absence of ceruloplasmin (Cp), a multicopper oxidase important for iron export. Few patients homozygous for loss of function mutations of the Cp gene have been reported. We describe a 62-year-old white woman with heavy liver iron overload, diabetes, anemia, and neurologic symptoms. She was compound heterozygote for 2 novel mutations that result in the absence of hepatocyte Cp: an adenine insertion at nucleotide 2917 causing a truncated protein and a C-G transversion causing a glutamine→glutamic acid substitution at position 146. Although rare in whites, aceruloplasminemia should be considered in the differential diagnosis of unexplained anemia associated with iron overload, because these features anticipate progressive neurologic symptoms. We propose that anemia, secondary to the impaired macrophage iron release, plays a major role in hepatic iron overload through increased absorption mediated by the erythroid regulator.
Prolongation of cardiac repolarization by arsenic trioxide
Authors: Chiang Chern-En , Luk Hsiang-Ning , Wang Tsui-Ming , Ding Philip Yu-An 
Published: August 2002

Abstract
Arsenic trioxide (As2O3; ATO) has recently been found to be very effective for relapsed acute promyelocytic leukemia. Several articles reported prolongation of QT interval or ventricular arrhythmias in patients receiving ATO. However, the QT-prolonging effect has not been confirmed and the direct membrane effect of ATO has never been studied. In the present investigation, using conventional action potential recording technique, we found that ATO dose dependently prolonged action potential duration (APD) in guinea pig papillary muscle with a slow pacing frequency. Parenteral administration of ATO prolonged QT interval and APD in guinea pig hearts. Intravenous infusion of clinically relevant doses of ATO prolonged QT interval and APD dose dependently. These studies suggest that ATO has a direct effect on cardiac repolarization. Patients who are receiving ATO should avoid concomitant administration of other QT-prolonging agents or conditions in favor of delaying cardiac repolarization.
Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors
Authors: Ng Andrea K. , Bernardo M. V. Patricia , Weller Edie , Backstrand Kendall , Silver Barbara , Marcus Karen C. , Tarbell Nancy J. , Stevenson Mary Ann , Friedberg Jonathan W. , Mauch Peter M. 
Published: August 2002

AbstractThe excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the long-term risks and temporal trends, identify patient- and treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P = .015). The risk increased with increasing radiation field size (P = .03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limited-field radiation therapy.
Effect of hyperhomocysteinemia on protein C activation and activity
Authors: Lentz Steven R. , Piegors Donald J. , Fernández José A. , Erger Rochelle A. , Arning Erland , Malinow M. René , Griffin John H. , Bottiglieri Teodoro , Haynes William G. , Heistad Donald D. 
Published: August 2002

AbstractHyperhomocysteinemia has been proposed to inhibit the protein C anticoagulant system through 2 mechanisms: decreased generation of activated protein C (APC) by thrombin, and resistance to APC caused by decreased inactivation of factor Va (FVa). We tested the hypotheses that generation of APC by thrombin is impaired in hyperhomocysteinemia in monkeys and that hyperhomocysteinemia produces resistance to APC in monkeys, mice, and humans. In a randomized crossover study, cynomolgus monkeys were fed either a control diet or a hyperhomocysteinemic diet for 4 weeks. Plasma total homocysteine (tHcy) was approximately 2-fold higher when monkeys were on the hyperhomocysteinemic diet than when they were on the control diet (9.8 ± 2.0 μM versus 5.6 ± 1.0 μM; P < .05). After infusion of human thrombin (25 μg/kg of body weight), the peak level of plasma APC was 136 ± 16 U/mL in monkeys fed the control diet and 127 ± 13 U/mL in monkeys fed the hyperhomocysteinemic diet (P > .05). The activated partial thromboplastin time was prolonged to a similar extent by infusion of thrombin in monkeys fed the control diet and in those fed the hyperhomocysteinemic diet. The sensitivity of plasma FV to human APC was identical in monkeys on control diet and those on hyperhomocysteinemic diet. We also did not detect resistance of plasma FV to APC in hyperhomocysteinemic mice deficient in cystathionine β-synthase (plasma tHcy, 93 ± 16 μM) or in human volunteers with acute hyperhomocysteinemia (plasma tHcy, 45 ± 6 μM). Our findings indicate that activation of protein C by thrombin and inactivation of plasma FVa by APC are not impaired during moderate hyperhomocysteinemia in vivo.
DNB: a partial D with anti-D frequent in Central Europe
Authors: Wagner Franz F. , Eicher Nicole I. , Jørgensen Jan R. , Lonicer Cornelie B. , Flegel Willy A. 
Published: August 2002

AbstractTo improve routine D typing and define transfusion strategy, it is important to establish the frequency of partial D alleles and their susceptibility to anti-D alloimmunization due to transfusion or pregnancy. We identified the partial D DNB that was caused by anRHD(G355S) allele associated with a CDehaplotype and whose phenotype presented a normal D in routine typing. The antigen density was about 6000 D antigens per red blood cell, and the Rhesus index was 0.02. Five anti-D immunization events with allo–anti-D titers up to 128 were observed. Twelve carriers of DNB were whites of Central Europe; the only Danish proband had Austrian ancestry. DNB was the most frequent partial D recognized so far in whites, occurring with frequencies of up to 1:292 in Switzerland. DNB was the underlying partial D phenotype in a relevant fraction of anti-D immunizations occurring in whites.
The caspase inhibitor z-VAD is more effective than CD18 adhesion blockade in reducing muscle ischemia-reperfusion injury: implication for clinical trials
Authors: Iwata Akiko , Harlan John M. , Vedder Nicholas B. , Winn Robert K. 
Published: August 2002

Abstract
Ischemia-reperfusion (I/R) leads to organ injury and organ dysfunction in a variety of clinical disorders. Preclinical investigations examining leukocyte adhesion molecules in I/R provided overwhelming evidence that blocking the function of leukocyte adhesion molecules would be highly effective in improving outcome in clinically relevant diseases. Unfortunately, all 9 of the recently completed phase 2 and 3 clinical trials examining antiadhesion therapy have failed. In this report, we show that a modest increase in ischemic time results in conversion from a CD18-dependent to a CD18-independent injury. This fundamental change in the mechanism of injury can be reduced by inhibition of caspases leading to blockade of apoptosis. Muscle injury resulting from aortic clamping was measured by release of creatine kinase. I/R injury following ischemia of 60 minutes or less and 3 hours of reperfusion was significantly reduced by pretreatment with anti-CD18 monoclonal antibody. However, 90 minutes of ischemia resulted in a marked increase in injury that was not reduced by CD18 blockade. Importantly, the injury resulting from 90 or 120 minutes of ischemia was reduced by the pancaspase inhibitor z-VAD. We propose that the length of ischemia can result in a fundamental change in the mechanism of injury and that all preclinical investigations of I/R must be evaluated with increasing ischemia if they are to model the clinical disease. The result showing CD18-independent I/R injury is not unique; likewise, protection by caspase inhibitors is not unique. However, we show for the first time that caspase inhibitors are effective when CD18 blockade is not.
A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover
Authors: de Haan Gerald , Bystrykh Leonid V. , Weersing Ellen , Dontje Bert , Geiger Hartmut , Ivanova Natalia , Lemischka Ihor R. , Vellenga Edo , Van Zant Gary 
Published: August 2002

AbstractHematopoietic stem cells from different strains of mice vary widely with respect to their cell cycle activity. In the present study we used complementary genetic and genomic approaches to identify molecular pathways affecting this complex trait. We identified a major quantitative trait locus (QTL) associated with variation in cell proliferation in C57BL/6 and DBA/2 mice to a 10 centimorgan (cM) region on chromosome 11. A congenic mouse model confirmed that a genomic interval on chromosome 11 in isolation confers the proliferation phenotype. To detect candidate genes we performed subtractive hybridizations and gene arrays using cDNA from highly enriched stem cells from parental strains. Intriguingly, a disproportionate number of differentially expressed genes mapped to chromosome 11 and, more specifically, these transcripts occurred in 3 distinct clusters. The largest cluster colocalized exactly with the cell cycling QTL. Such clustering suggested the involvement of genetic variation that affects higher-order chromosomal organization. This hypothesis was reinforced by the fact that differentially expressed genes mapped to recombination “coldspots,” as a consequence of which clustered genes are collectively inherited. These findings suggest the functional interdependence of these closely linked genes. Our data are consistent with the hypothesis that this isolated cell cycle QTL does not result from a mutation in a single gene but rather is a consequence of variable expression of a collection of highly linked genes.
Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome
Authors: Kanaji Taisuke , Russell Susan , Ware Jerry 
Published: August 2002

AbstractAn absent platelet glycoprotein (GP) Ib-IX receptor results in the Bernard-Soulier syndrome and is characterized by severe bleeding and the laboratory presentation of macrothrombocytopenia. Although the macrothrombocytopenic phenotype is directly linked to an absent GP Ib-IX complex, the disrupted molecular mechanisms that produce the macrothrombocytopenia are unknown. We have utilized a mouse model of the Bernard-Soulier syndrome to engineer platelets expressing an α-subunit of GP Ib (GP Ibα) in which most of the extracytoplasmic sequence has been replaced by an isolated domain of the α-subunit of the human interleukin-4 receptor (IL-4Rα). The IL-4Rα/GP Ibα fusion is membrane expressed in Chinese hamster ovary (CHO) cells, and its expression is facilitated by the presence of human GP IX and the β-subunit of GP Ib. Transgenic animals expressing a chimeric receptor were generated and bred into the murine Bernard-Soulier syndrome–producing animals devoid of mouse GP Ibα but expressing the IL-4Rα/GP Ibα fusion sequence. The characterization of these mice revealed a 2-fold increase in circulating platelet count and a 50% reduction in platelet size when compared with platelets from the mouse model of the Bernard-Soulier syndrome. Immunoprecipitation confirmed that the IL-4Rα/GP Ibα subunit interacts with filamin-1 and 14-3-3ζ, known binding proteins to the GP Ibα cytoplasmic tail. Mice expressing the chimeric receptor retain a severe bleeding phenotype, confirming a critical role for the GP Ibα extracytoplasmic domain in hemostasis. These results provide in vivo insights into the structural elements of the GP Ibα subunit that contribute to normal megakaryocyte maturation and thrombopoiesis.
Hydrocortisone reduced in vivo, inflammation-induced slow rolling of leukocytes and their extravasation into human conjunctiva
Authors: Kirveskari Juha , Helintö Maaret , Moilanen Jukka A. O. , Paavonen Timo , Tervo Timo M. T. , Renkonen Risto 
Published: August 2002

AbstractHydrocortisone reduces the number of inflammatory leukocytes within tissues, but thus far the site of action on the multistep adhesion cascade leading to leukocyte extravasation has not been identified. We have recently developed a noninvasive in vivo reflected-light confocal microscopy technique to study this at sites of inflammation in human patients. In the present study, we evaluated the effect of preoperative intravenous hydrocortisone treatment on leukocyte trafficking after conjunctival inflammation induced by cataract surgery in human subjects in vivo. The surgery generated leukocyte rolling along the endothelial lining of conjunctival vessels. While preoperative hydrocortisone did not reduce the number of rolling cells, it significantly raised the velocity of individual rolling leukocytes and concomitantly reduced leukocyte emigration into conjunctival tissue. Immunohistology of conjunctival biopsies excised from the individuals studied provided circumstantial evidence that endothelial P-selectin might play a role in the surgery-induced up-regulation of the leukocyte rolling. Furthermore, hydrocortisone reduced surgery-induced P-selectin induction, suggesting a role for this selectin in the regulation of local leukocyte traffic into sites of inflammation in human conjunctiva. Taken together, these results suggest that control of the rolling velocity might be an effective way to adjust leukocyte traffic in vivo in human subjects.
Narrative and severe mental illness: what place do stories have in an evidence-based world?
Authors: Roberts Glenn A. 
Published: August 2002

“Once the patient's biography becomes part of the care, the possibility that therapy will dehumanise the patient, stripping him of what is unique to his illness experience becomes much less likely” (Kleinman, 1988).“The loss of story making and telling has its impact on failure to care for the long term chronic or incurable patient” (Hunter, 1991).
Psychiatric implications of chronic civilian strife or war: Northern Ireland
Authors: Curran Peter S. , Miller Paul W. 
Published: August 2002

“Sectarianism lives in all of us – it is in the choices we make, it is in the words we say, it is even in the friends we make. It lives in our churches and it taints our community life. It makes possible the violent actions which we abhor” (McKittrick et al, 1999).As Northern Ireland celebrates the first year in 30 years when a soldier or police officer has not been killed and as it currently struggles to implement yet another political initiative to gain peace, now seems an appropriate time to reflect upon the effect of political violence on the psychiatric services in the province. For almost two generations the campaign of political violence has touched every doctor professionally. Indeed, one of us was a houseman in the front line Royal Victoria Hospital and the other was just born when the sectarian street pogroms and internecine violence first erupted. Neither of us knew that what was to follow would determine our professional futures. In the fresh air of the new millennium, and particularly following the horror of the Omagh massacre of August 1998 and the hope of the Good Friday agreement of April 1998, we can reflect upon and review the psychiatric aspects of politically inspired violence.
Murmurs of discontent: treatment and treatability of personality disorder
Authors: Adshead Gwen 
Published: August 2002

“They murmured, as they took their fees ‘There is no cure for this disease’.”Hilaire BellocTreatability is a confused and confusing concept in psychiatry. In its legal sense, it is a measure that limits the involuntary admission of patients with some particular types of mental disorder. The legal term itself has generated considerable discussion and dissent (e.g. Mawson, 1983; Grounds, 1987), and the Government's White Paper on reforming mental health legislation in England and Wales proposes to abolish it (Department of Health, 2000).
Premenstrual syndrome: an update on definitions, diagnosis and management
Authors: Connolly Moira 
Published: August 2002

Most articles on the management of the premenstrual syndrome (PMS) begin by noting that the term “premenstrual tension” was first coined by R. T. Frank in 1931 and “pre-menstrual syndrome” by Greene & Dalton in 1953. However, in 1847, Dr Ernst F. von Feuchtersleben wrote:
“The menses in sensitive women is almost always attended by mental uneasiness, irritability and sadness.” (quoted by Rubinow & Schmidt, 1995)
Home assessments in old age psychiatry
Authors: Richardson Barbora , Orrell Martin 
Published: August 2002

“For people to be successfully supported at home, a comprehensive assessment is an essential first step.” (Audit Commission, 2000: p. 43.)Home visits by old age psychiatrists remain popular with elderly patients, their carers and general practitioners (GPs). Home assessments by various disciplines working with older people have been endorsed as a sign of good practice by the Audit Commission (2000) in their recent national report on mental health services for older people:
“Assessment at home is often better as people are most likely to behave and communicate in their normal way in familiar surroundings. Staff can also build a more accurate picture of people's needs and learn the views of their carers. Professionals can observe whether there is adequate food in the house, whether people can make themselves a hot drink, and whether there are any likely risks from poor hygiene or fire hazards.” (Audit Commission, 2000: p. 43.)
Outcome research in family therapy
Authors: Asen Eia 
Published: August 2002

The family and therapyThe term family therapy can be misleading. ‘Family’ is open to many interpretations, if not attacks, because it is frequently read as implying a two-parent, heterosexual couple with two children, with the woman primarily the ‘homemaker’ and the man the ‘breadwinner’, with occasional backup from the grandparents. Such a picture would seem to marginalise or exclude other family forms, such as childless couples, single parents with children, gay or lesbian couples and unattached elderly persons. However, the reality is that family therapists treat many different forms of committed relationships and friendships. As to the term therapy, it tends to imply the presence of illness or dysfunction, located in the family rather than one of its individual members, and may thus be quite unacceptable to families who often believe that it is the patient and not them whom requires help. Being at the receiving end of family therapy can have strong connotations of blame. Practitioners therefore increasingly use the term systemic therapy, which is also more informative because some of the work often involves the wider system. The systemic approach is essentially a contextual approach – seeing and treating people in context.
Implications for psychiatric services of chronic civilian strife: young refugees in the UK
Authors: Hodes Matthew 
Published: August 2002

Over the past century war and organised violence have led to the displacement of large populations and threatened or resulted in genocide of many ethnic or cultural groups. Although many people are internally displaced within their own country, some flee and seek asylum in other countries. The United Nations High Commission on Refugees (UNHCR) defines a refugee as someone who:
‘Owing to well-founded fear of being persecuted for reasons of race, religion, nationality, membership of a particular social group or political opinion, is outside the country of his nationality and is unable or, owing to such fear, is unwilling to avail himself of the protection of that country; or who, not having a nationality and being outside that country of his former habitual residence as a result of such events, is unable or, owing to such fear, is unwilling to return to it’ (UNHCR, 1951: Article 1A(2)).
Genetics advances and learning disability
Authors: Muir Walter J. 
Published: August 2002

BackgroundMedicine is rapidly becoming molecular medicine, and little escapes the grasp of modern genetics. Most disorders associated with learning disability have at least a genetic component influencing their expression; in many disorders, disturbances of genetic mechanisms play a pivotal role.AimsDynamic mutations, imprinting mechanisms and gene-dosage effects are explained with reference to genetic disorders that lead to learning disability.MethodA review of recent important studies in the genetics of learning disability.ResultsA host of new genetic connections to conditions associated with learning disability have been made.ConclusionsA basic understanding of these genetic connections is important for all learning disability psychiatrists if they are to follow the rapid changes – already beginning to influence our practice – that hold immense promise for the future.