bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Initial Soil Moisture on Rainfall Generation and Subsequent Hydrologic Response during the North American Monsoon
Authors: Vivoni Enrique R. , Tai Kinwai , Gochis David J. 
Published: December 2008

Abstract
Through the use of a mesoscale meteorological model and distributed hydrologic model, the effects of initial soil moisture on rainfall generation, streamflow, and evapotranspiration during the North American monsoon are examined. A collection of atmospheric fields is simulated by varying initial soil moisture in the meteorological model. Analysis of the simulated rainfall fields shows that the total rainfall, intensity, and spatial coverage increase with higher soil moisture. Hydrologic simulations forced by the meteorological fields are performed using two scenarios: (i) fixed soil moisture initializations obtained via a drainage experiment in the hydrologic model and (ii) adjusted initializations to match conditions in the two models. The scenarios indicate that the runoff ratio increases with higher rainfall, although a change is observed from a linear (fixed initialization) to a nonlinear response (adjusted initialization). Variations in basin response are attributed to controls exerted by rainfall, soil, and vegetation properties for varying initial conditions. Antecedent wetness significantly influences the runoff response through the interplay of different runoff generation mechanisms and also controls the evapotranspiration process. The authors conclude that a regional increase in initial soil moisture promotes rainfall generation, streamflow, and evapotranspiration for this warm-season case study.
Paroxysmal Nocturnal Hemoglobinuria: Stem Cells and Clonality
Authors: Brodsky Robert A. 
Published: December 2008

AbstractParoxysmal nocturnal hemoglobinuria is a clonal hematopoietic stem cell disease that manifests with intravascular hemolysis, bone marrow failure, thrombosis, and smooth muscle dystonias. The disease can arise de novo or in the setting of acquired aplastic anemia. All PNH patients to date have been shown to harbor PIG-A mutations; the product of this gene is required for the synthesis of glycosylphosphatidylinositol (GPI) anchored proteins. In PNH patients, PIG-A mutations arise from a multipotent hematopoietic stem cell. Interestingly, PIG-A mutations can also be found in the peripheral blood of most healthy controls; however, these mutations arise from progenitor cells rather than multipotent hematopoietic stem cells and do not propagate the disease. The mechanism of whereby PNH stem cells achieve clonal dominance remains unclear. The leading hypotheses to explain clonal outgrowth in PNH are: 1) PNH cells evade immune attack possibly, because of an absent cell surface GPI-AP that is the target of the immune attack; 2) The PIG-A mutation confers an intrinsic resistance to apoptosis that becomes more conspicuous when the marrow is under immune attack; and 3) A second mutation occurs in the PNH clone to give it an intrinsic survival advantage. These hypotheses may not be mutually exclusive, since data in support of all three models have been generated.
Late Pulmonary, Cardiovascular, and Renal Complications after Hematopoietic Stem Cell Transplantation and Recommended Screening Practices
Authors: Tichelli André , Rovó Alicia , Gratwohl Alois 
Published: December 2008

Abstract
Non-malignant late effects after hematopoietic stem cell transplantation (HSCT) are heterogeneous in nature and intensity. The type and severity of the late complications depend on the type of transplantation and the conditioning regimen applied. Based on the most recent knowledge, we discuss three typical non-malignant complications in long-term survivors after HSCT, namely pulmonary, cardiovascular and renal complications. These complications illustrate perfectly the great diversity in respect of frequency, time of appearance, risk factors, and outcome. Respiratory tract complications are frequent, appear usually within the first two years, are closely related to chronic graft-versus-host disease (GVHD) and are often of poor prognosis. Cardiac and cardiovascular complications are mainly related to cardiotoxic chemotherapy and total body irradiation, and to the increase of cardiovascular risk factors. They appear very late after HSCT, with a low magnitude of risk during the first decade. However, their incidence might increase significantly with longer follow-up. The chronic kidney diseases are usually asymptomatic until end stage disease, occur within the first decade after HSCT, and are mainly related with the use of nephrotoxic drugs such as calcineurin inhibitors. We will discuss the practical screening recommendations that could assist practitioner in the follow-up of long-term survivors after HSCT.
The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism
Authors: Fleming Mark D. 
Published: December 2008

AbstractSystemic iron homeostasis depends on the regulated expression of hepcidin, a peptide hormone that negatively regulates iron egress from intestinal cells and macrophages by altering the expression of the cellular iron exporter ferroportin. In doing so, hepcidin can control both the total body iron by modulating intestinal iron absorption as well as promote iron available for erythropoiesis by affecting the efficiency with which macrophages recycle iron from effete red blood cells. This review focuses on the systemic and cellular physiology of hepcidin regulation in relation to iron stores, erythropoiesis, inflammation, and hypoxia and how hepcidin regulation and dysregulation contributes to normal iron homeostasis and iron metabolism disorders.
Gene Replacement Therapy for Sickle Cell Disease and Other Blood Disorders
Authors: Townes Tim M. 
Published: December 2008

Abstract
Previous studies have demonstrated that sickle cell disease (SCD) can be corrected in mouse models by transduction of hematopoietic stem cells with lentiviral vectors containing anti-sickling globin genes followed by transplantation of these cells into syngeneic recipients. Although self-inactivating (SIN) lentiviral vectors with or without insulator elements should provide a safe and effective treatment in humans, some concerns about insertional mutagenesis persist. An ideal correction would involve replacement of the sickle globin gene (βS) with a normal copy of the gene (βA). We recently derived embryonic stem (ES) cells from a novel knockin mouse model of SCD and tested a protocol for correcting the sickle mutation by homologous recombination. Animals derived after gene replacement produced high levels of normal human hemoglobin (HbA), and the pathology associated with SCD was corrected. These experiments provided a foundation for similar studies in which our group collaborated with Rudolf Jaenisch’s laboratory to correct SCD by gene replacement in iPS (induced pluripotent stem) cells derived by direct reprogramming of sickle skin fibroblasts. Corrected iPS cells were differentiated into hematopoeitic progenitors that were transplanted into irradiated sickle recipients. The transplanted animals produced high levels of normal human HbA, and the pathology of SCD was corrected. These proof-of-principle studies provide a foundation for the development of gene replacement therapy for human patients with SCD and other blood disorders.
Which Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Should Be Treated with Eculizumab?
Authors: Haspel Richard L. , Hillmen Peter 
Published: December 2008

Abstract
A 45-year-old woman presents for evaluation as a result of persistent anemia. Ultimately, she is diagnosed with hemolytic anemia ascribed to paroxysmal nocturnal hemoglobinuria. She is otherwise well and has an otherwise normal complete blood cell count. She requires transfusion about once every 6 weeks for symptomatic anemia. She wonders whether she would benefit from eculizumab.
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia When a Matched Related Donor Is Not Available
Authors: Appelbaum Frederick R. 
Published: December 2008

AbstractAlthough for many patients with acute myeloid leukemia (AML) allogeneic hematopoietic cell transplantation (HCT) from a matched related donor provides the best, and sometimes the sole chance for cure, only about 30% of individuals have HLA-matched family members. Fortunately, recent advances on a number of fronts have expanded the acceptable donor pool. With the use of high-resolution typing, HCT outcomes using unrelated donors matched at HLA-A, -B, -C and -DRB1 give results very similar to those expected with matched related donors. A single mismatch, as determined either by low- or high-resolution testing, results in modestly worse outcomes, with mismatches at B or C better tolerated than mismatches at A or DRB1. Initial results of umbilical cord blood transplantation for adults showed a clear association of cell dose and outcome, limiting the procedure to a minority of adults where cord bloods with at least 2.5 or 3 × 107 total nucleated cells/kg could be found. More recently, the use of double cord transplants has shown considerable promise, lowering the risk of graft rejection and possibly the risk of relapse as well. Haploidentical transplantation using T-cell–replete marrow and post-transplant high-dose cyclophosphamide, or T-cell–depleted peripheral blood and marrow containing high doses of CD34+ cells is under investigation. Together, these various approaches are broadening the transplant options for patients with AML.
MDS: A Stem Cell Disorder—But What Exactly Is Wrong with the Primitive Hematopoietic Cells in This Disease?
Authors: Nimer Stephen D. 
Published: December 2008

Abstract
Despite the various abnormalities identified in the immune system or the bone marrow microenvironment in patients with myelodysplastic syndrome (MDS), most of the investigation of this disorder has centered on the hematopoietic stem/progenitor compartment. It is generally written that MDS is a stem cell disorder, and there is certainly evidence supporting this view. However, whether it occurs in a cell with only myeloid multipotentiality (i.e., that involves megakaryocytic, erythroid and granulocytic/monocytic lineages) or occurs in a true stem cell is open to debate. The absence of an assay for human stem cells necessitates the use of surrogate markers for such cells, such as gene expression profiles, or the identification of specific genetic or epigenetic abnormalities that are found in multiple lineages. Clearly, the common cytogenetic and genetic abnormalities found in MDS are most indicative of a clonal myeloid disease similar to AML, rather than a lymphoid disease, and the often tri-lineage ineffective hematopoiesis and dysplasia are generally not found within the lymphoid compartment. Recent studies, using modern molecular detection techniques, have identified new recurring molecular lesions in these disorders but have not really unraveled its pathogenesis.
Molecular Profiling in CLL
Authors: Gribben John G. 
Published: December 2008

Abstract
Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, with some patients requiring immediate therapy and others living without need for treatment for decades. There has been considerable interest in the underlying molecular mechanisms of this heterogeneity to understand not only the expected clinical course for individual patients but also the underlying pathogenesis of this disease. A number of clinical parameters have been identified that are predictive of the clinical course. More recently, a number of molecular biomarkers, most notably cytogenetics by fluorescent in situ hybridization (FISH), immunoglobulin heavy chain (IgVH) mutational status and expression of ZAP70, have been identified and verified as also providing prognostic information. The current challenge is to understand how we should use this new information in clinical practice and whether we should alter treatment based upon the detection of “high-risk” features. Over the past decade there has been considerable progress in development of more effective treatments for CLL, but current consensus is that treatment of CLL should be based upon the treatment of symptomatic disease. Specific treatment decisions based upon the detection of “high-risk” features remains a question for clinical trials, which will address the potential value of early treatment for specific groups of patients and whether all patients with CLL should receive a standard treatment or whether treatment should be modified in different risk groups.
Epigenetic Modulation and Other Options to Improve Outcome of Stem Cell Transplantation in MDS
Authors: Kröger Nicolaus 
Published: December 2008

AbstractAllogeneic stem cell transplantation can cure patients with myelodysplastic syndromes. However, more than 50% of the patients who underwent allogeneic stem cell transplantation have failed to benefit from this treatment approach either due to treatment-related mortality or to relapse. The introduction of toxicity or dose-reduced conditioning has significantly reduced the treatment-related mortality but did not affect the risk of relapse. New effective drugs, such as hypomethylating agents, histone-deacetylase inhibitors or lenalidomide, can be used alone or in combination to improve the pretransplant remission status before allogeneic stem cell transplantation or after transplantation to prevent relapse as maintenance or consolidation therapy. This review will focus on these new possibilities and give some perspectives as to how the results of allogeneic stem cell transplantation can be further improved
New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia
Authors: Levine Ross L. , Heaney Mark 
Published: December 2008

Abstract
Essential thrombocythemia (ET) is a hematopoietic disorder that manifests clinically as thrombocytosis, and patients with ET are at increased risk for developing thrombosis, myelofibrosis, and transformation to acute myeloid leukemia. Although ET was recognized as a distinct clinical syndrome more than 6 decades ago and was classified as a myeloproliferative neoplasm (MPN) by William Dameshek in 1951, the molecular pathogenesis of ET remained unknown until 2005, when activating mutations in the JAK2 tyrosine kinase (JAK2V617F) were identified in a significant proportion of patients with ET, polycythemia vera (PV) and primary myelofibrosis (PMF). In addition, subsequent studies have identified gain-of-function mutations in the thrombopoietin receptor (MPL) in a subset of patients with JAK2V617F-negative ET, suggesting that JAK2 activation by distinct mechanisms contributes to the pathogenesis of ET. Despite these important observations, important questions remain regarding the role of JAK2/MPL mutations in ET pathogenesis, the etiology of JAK2/MPL negative ET, the factors that distinguish ET from other MPNs with the JAK2V617F mutation, and the role of JAK2-targeted therapies for the treatment of these MPNs.
Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke
Authors: Yukiiri Kazushi , Hosomi Naohisa , Naya Takayuki , Takahashi Tsutomu , Ohkita Hiroyuki , Mukai Mao , Masugata Hisashi , Murao Koji , Ueno Masaki , Nakamura Takehiro , Dobashi Hiroaki , Miki Takanori , Kuroda Yasuhiro , Kohno Masakazu 
Published: December 2008

Abstract

Background
Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patient's clinical variables.

Methods
Our patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.

Results
Plasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F4,126 = 27.6, p < 0.0001; adjusted R2 = 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ2 = 127.5, p < 0.001).

Conclusion
It was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.
THE SIGNIFICANCE OF LYMPHADENOID CHANGES IN THE THYROID GLAND
Authors: GREENE R. 
Published: December 2008

In a series of 161 patients subjected to thyroidectomy, two were found to be suffering from Hashimoto's disease, and the thyroids of a further forty-two contained lymphadenoid nodules indistinguishable from those found in Hashimoto's disease. Of the forty-four patients whose glands showed the characteristic change, it was possible to follow in detail the post-operative course of forty-three. Of these, twenty developed severe hypothyroidism necessitating treatment with thyroid, while a further seven are under suspicion. Of the 117 patients whose glands did not show the characteristic change, none developed hypothyroidism.
The hypothesis is advanced that those patients with toxic goitres which are found to contain lymphadenoid nodules are suffering from early Hashimoto's disease.
THE EFFECTS OF OESTRADIOL ON THE RAT UTERUS
Authors: COLE D. F. 
Published: December 2008

1. The water and electrolyte changes in the uteri of spayed rats have been investigated after the administration of oestradiol-17 (β) and are found to fall into two main phases.
2. 6–10 hr. after the subcutaneous injection of the hormone the total water content increases, as a result of expansion of the extracellular fluid space and of the relative cell volume. The increase of the relative cell volume is caused by an increase of the idiomolar value.
3. 18–54 hr. after the injection the total water content increases again after a temporary fall. The water increase is now confined to the intracellular space. Total nucleoprotein and residual phosphorus increase, and it is suggested that the nucleoprotein phosphate groups are responsible for the increase of the electrostatic equivalent and hence the increased potassium concentration in the cells. The idiomolar value falls, and there is probably an increased formation of cell protein at this stage.
4. The changes observed in the total water content of the organ agree with the findings of Astwood [1938], Talbot, Lowrie & Astwood [1940] and Zuckerman, Palmer & Hanson [1950]. There are no significant changes in the plasma concentrations of potassium, sodium or chloride or in the total osmotic pressure of the plasma.
RECOVERY FROM OESTROGEN-INDUCED STERILITY IN ALBINO MICE
Authors: EMMENS C. W. 
Published: December 2008

1. Male albino mice were rendered sterile by the injection of 2·5–40 μg. of oestradiol benzoate in nut oil B.P. twice weekly. Seven out of eight mice were sterile after 6 weeks of injections of 10 μg. Testicular damage was seen histologically in some males, and a highly significant weight loss occurred in the testes of all groups. These effects rapidly disappeared when injections ceased, and full fertility and normal testicular weight were regained.
2. The control groups of males in these tests, while showing no testicular abnormalities, lost fertility to some extent when injected with either nut oil or physiological saline. This loss was also regained when injections ceased.
3. Female albino mice were rendered sterile by the injection of 0·5–12·5 μg. of oestradiol benzoate in nut oil twice weekly for 4 weeks. Even the lowest dose caused complete sterility during the period of injections and for 2 weeks thereafter. Recovery from all dose levels was apparently complete, although mice receiving 12·5 μg. took from 41 to 125 days to produce a litter when injections were stopped.
OBSERVATIONS ON THE INTRAVAGINAL ASSAY OF NATURAL OESTROGENS USING AQUEOUS EGG ALBUMIN AS THE VEHICLE OF ADMINISTRATION
Authors: BIGGERS J. D. 
Published: December 2008

1. Oestrone dissolved in 1 % aqueous albumin, and administered by the intravaginal route, has 2·5–4·9 times the activity shown in 50% aqueous glycerol. 1 % aqueous egg albumin alone does not produce cornification of the vagina in the mouse.
2. When administered in 1 % aqueous egg albumin the relative potency of oestriol in terms of oestrone is 1·09, limits of error (P = 0·05) 0·70–1·70; and that of oestradiol-3:17β is 1·75, limits of error (P = 0·05) 1·15–2·66.
3. The slopes of the dose-response lines obtained with albumin are lower than the slopes obtained with glycerol but tests show the difference to be not quite significant at the 5 % level. There is no doubt, however, that the intravaginal route in general gives a lower slope than the subcutaneous route.
4. The slopes of the dose-response lines obtained in intravaginal tests using oestrone, oestriol and oestradiol-3:17β do not differ significantly.
5. The observed differences in slope have been discussed from the point of view of oestrogen action.
APPLICATION OF ENDOCRINOLOGICAL RESEARCH METHODS IN PSYCHIATRY
Authors: REISS M. 
Published: December 2008

The difficulties involved in any analysis of neuro-endocrine relationships are outlined. Whether disturbances arise primarily in the brain or in the endocrine system the series of repercussions usually results in a vicious circle which has to be broken at some point if therapy is to be tried.
Hormone therapy of psychiatric cases has fallen into discredit because of its wide and indiscriminate use. Such treatment is only justified when the most exact and exhaustive tests of endocrine function have first been carried out. A number of such tests are discussed.
Investigation of 131I metabolism of the thyroid makes it possible to detect borderline cases with only very slight (previously unsuspected) thyroid disturbances. In many such cases the correct treatment of the thyroid under- or over-function improves the mental condition. Insensitivity of the body tissues to thyroid hormone is assumed in cases where the radioactive tracer method shows an increased thyroid function while the B.M.R. is normal or decreased.
The use of ACTH for clinical response tests for the adrenal cortex and for treatment of different mental cases is discussed, together with gonadal and pituitary anterior lobe function in its relation to mental disorder.
Different psychopathological states can develop under identical endocrine conditions; different endocrine changes can be seen in cases which are to the psychiatrist 'identical entities'. The classical conception of psychiatric entities must be considered out of date if pathogenetic and causal analysis of mental disease is to be established.