bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study
Authors: Joshi Deval D. , Dang Anju , Yadav Prem , Qian Jing , Bandari Persis S. , Chen Kunhua , Donnelly Robert , Castro Tammy , Gascon Pedro , Haider Ali , Rameshwar Pranela
Published: July 2002

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)–β and tumor necrosis factor–α in BM stroma. TGF–β production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.
Differential gene expression profiling of adult murine hematopoietic stem cells
Authors: Park In-Kyung , He Yaqin , Lin Fangming , Laerum Ole D. , Tian Qiang , Bumgarner Roger , Klug Christopher A. , Li Kaijun , Kuhr Christian , Doyle Michelle J. , Xie Tao , Schummer Michèl , Sun Yu , Goldsmith Adam , Clarke Michael F. , Weissman Irving L. , Hood Leroy , Li Linheng
Published: July 2002

Hematopoietic stem cells (HSCs) have self-renewal capacity and multilineage developmental potentials. The molecular mechanisms that control the self-renewal of HSCs are still largely unknown. Here, a systematic approach using bioinformatics and array hybridization techniques to analyze gene expression profiles in HSCs is described. To enrich mRNAs predominantly expressed in uncommitted cell lineages, 54 000 cDNA clones generated from a highly enriched population of HSCs and a mixed population of stem and early multipotent progenitor (MPP) cells were arrayed on nylon membranes (macroarray or high-density array), and subtracted with cDNA probes derived from mature lineage cells including spleen, thymus, and bone marrow. Five thousand cDNA clones with very low hybridization signals were selected for sequencing and further analysis using microarrays on glass slides. Two populations of cells, HSCs and MPP cells, were compared for differential gene expression using microarray analysis. HSCs have the ability to self-renew, while MPP cells have lost the capacity for self-renewal. A large number of genes that were differentially expressed by enriched populations of HSCs and MPP cells were identified. These included transcription factors, signaling molecules, and previously unknown genes.
Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity
Authors: Oostendorp Robert A. J. , Harvey Kirsty N. , Kusadasi Nuray , de Bruijn Marella F. T. R. , Saris Chris , Ploemacher Rob E. , Medvinsky Alexander L. , Dzierzak Elaine A.
Published: July 2002

The aorta-gonads-mesonephros (AGM) region autonomously generates the first adult repopulating hematopoietic stem cells (HSCs) in the mouse embryo. HSC activity is initially localized to the dorsal aorta and mesenchyme (AM) and vitelline and umbilical arteries. Thereafter, HSC activity is found in the urogenital ridges (UGs), yolk sac, and liver. As increasing numbers of HSCs are generated, it is thought that these sites provide supportive microenvironments in which HSCs are harbored until the bone marrow microenvironment is established. However, little is known about the supportive cells within these midgestational sites, and particularly which microenvironment is most supportive for HSC growth and maintenance. Thus, to better understand the cells and molecules involved in hematopoietic support in the midgestation embryo, more than 100 stromal cell lines and clones were established from these sites. Numerous stromal clones were found to maintain hematopoietic progenitors and HSCs to a similar degree as, or better than, previously described murine stromal lines. Both the AM and UG subregions of the AGM produced many supportive clones, with the most highly HSC-supportive clone being derived from the UGs. Interestingly, the liver at this stage yielded only few supportive stromal clones. These results strongly suggest that during midgestation, not only the AM but also the UG subregion provides a potent microenvironment for growth and maintenance of the first HSCs.
In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis
Authors: Claessens Yann-Erick , Bouscary Didier , Dupont Jean-Michel , Picard Françoise , Melle Josiane , Gisselbrecht Sylvie , Lacombe Catherine , Dreyfus François , Mayeux Patrick , Fontenay-Roupie Michaëla
Published: July 2002

Erythropoiesis results from the proliferation and differentiation of pluripotent stem cells into immature erythroid progenitors (ie, erythroid burst-forming units (BFU-Es), whose growth, survival, and terminal differentiation depends on erythropoietin (Epo). Ineffective erythropoiesis is a common feature of myelodysplastic syndromes (MDS). We used a 2-step liquid-culture procedure to study erythropoiesis in MDS. CD34+ cells from the marrow of patients with MDS were cultured for 10 days in serum-containing medium with Epo, stem cell factor, insulinlike growth factor 1, and steroid hormones until they reached the proerythroblast stage. The cells were then placed in medium containing Epo and insulin for terminal erythroid differentiation. Numbers of both MDS and normal control cells increased 103fold by day 15. However, in semisolid culture, cells from patients with refractory anemia (RA) with ringed sideroblasts and RA or RA with excess of blasts produced significantly fewer BFU-Es than cells from controls. Fluorescence in situ hybridization analysis of interphase nuclei from patients with chromosomal defects indicated that abnormal clones were expanded in vitro. Epo-signaling pathways (STAT5, Akt, and ERK 1/2) were normally activated in MDS erythroid progenitors. In contrast, apoptosis was significantly increased in MDS cells once they differentiated, whereas it remained low in normal cells. Fas was overexpressed on freshly isolated MDS CD34+ cells and on MDS erythroid cells throughout the culture. Apoptosis coincided with overproduction of Fas ligand during the differentiation stage and was inhibited by Fas-Fc chimeric protein. Thus, MDS CD34+-derived erythroid progenitors proliferated normally in our 2-step liquid culture with Epo but underwent abnormal Fas-dependent apoptosis during differentiation that could be responsible for the impaired erythropoiesis.
Ph+ acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation
Authors: Hofmann Wolf-K. , Jones Letetia C. , Lemp Nathan A. , de Vos Sven , Gschaidmeier Harald , Hoelzer Dieter , Ottmann Oliver G. , Koeffler H. Phillip
Published: July 2002

The tyrosine kinase inhibitor STI571 is a promising agent for the treatment of advanced Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), but resistance develops rapidly in most patients after an initial response. To identify mechanisms of resistance to STI571, 30 complementary DNAs (including 9 matched samples) obtained from the bone marrow of individuals with Ph+ ALL were analyzed by direct sequencing of a 714–base pair region of ABL encoding for the adenosine triphosphate (ATP)–binding site and the kinase activation loop. A single point mutation was found at nucleotide 1127 (GI6382056) resulting in Glu255Lys. This mutation occurred in 6 of 9 patients (67%) following their treatment with STI571 but not in the samples from patients before beginning treatment with STI571. Glu255Lys is within the motif important for forming the pocket of the ATP-binding site in ABL and it is highly conserved across species. In conclusion, Ph+ ALL samples resistant to STI571 have a unique mutation Glu255Lys of BCR-ABL.
Development of a felled seam monitoring device
Authors: Clapp Timothy G. , Martin Benjamin R.
Published: July 2002

This paper discusses the electrical design of a seam monitoring device for felled seams. Felled seams are commonly found in commercial products, such as apparel garments, parachutes, tenting and geotextiles. The felled seam can be improperly formed during the seaming process, producing defects that may not be detected by visual inspection. The felled seam monitoring device ensures the detection of a faulty felled seam during the seam formation process. The design focuses on the utilization of inexpensive electronic technology and analysis of displacement-based sampling techniques to meet apparel manufacturer’s design specifications.
Power system stabilizer based on a self-learning adaptive network fuzzy inference system
Authors: Malik O. P. , Hariri A.
Published: July 2002

Application of a self-learning adaptive network-based fuzzy inference system as a power system stabilizer (PSS) is described in this paper. A multilayer adaptive network is employed to design the fuzzy logic controller with self-learning capability that does not require another controller to tune the fuzzy inference rules and membership functions. Details of the design process are given. Behaviour of the proposed PSS, investigated under different operating conditions and disturbances in both simulation and real-time tests, illustrates its effectiveness in providing enhanced damping of the power system oscillations.
A multiobjective-optimal neuro-fuzzy extension to power plant co-ordinated control
Authors: Garduno-Ramirez Raul , Lee Kwang Y.
Published: July 2002

This paper presents an overall control scheme for wide-range multiobjective-optimal operation of a fossil-fuel power unit. The scheme provides the means to accommodate operating scenarios characterized by multiple operating requirements, and to attain optimal operation along any arbitrary unit load-demand pattern. The proposed strategy builds upon current co-ordinated control schemes, which typically account for simultaneous control of power and steam pressure. First, the scope of co-ordination over the internal processes of the unit is extended by including the control of the drum water level to achieve balanced overall plant operation at all loads. Then, a supervisory reference governor and a neuro-fuzzy feedforward control path are added to complement the already existing multiloop feedback control configuration. The reference governor implements a set-point scheduler based on unit load demand to set-point mappings, which are designed by solving a multiple objective optimization problem. The feedforward control path approximates the nonlinear multivariable inverse static behaviour of the power unit at the optimal operating conditions specified by the set-point mappings through a set of multi-input-single-output fuzzy inference systems, which are designed using a neuro-fuzzy learning paradigm. With this approach, the plant is driven by an arbitrary unit load-demand pattern from which the reference governor specifies the multiobjective-optimal operating conditions for the plant through set-point trajectories; the feedforward control path provides control signals to achieve wide-range manoeuvrability and the feedback control path compensates for uncertainties and disturbances, along and around the commanded set-point trajectories, respectively. Simulation results demonstrate the feasibility of the proposed control scheme.
Lifestyle risks for three disease outcomes in spinal cord injury
Authors: Davies Diane S , McColl Mary Ann
Published: July 2002

Object: The majority of research focusing on lifestyle risks in the spinal cordinjured population to date has mainly been descriptive in nature. Limited research has examined the relationships between lifestyle risks and morbidity. This study was undertaken to quantify the associations between selected lifestyle risks and morbidity associated with three top causes of mortality in adults with spinal cord injury (SCI).

Method: Ninety-seven adults who had incurred a spinal cord injury between 1972 and 1992 were interviewed over the telephone to assess morbidity and lifestyle exposure history. Logistic regression modelling was used to assess the association between lifestyle risks and cardiovascular, respiratory and urinary tract disorders.

Results: Risk of cardiovascular morbidity was found to be positively associated with age and duration of cigarette use. Risk of respiratory morbidity was found to be positively associated with quadriplegia, number of cigarettes smoked per day, and the interaction between cigarettes smoked per day and excessive alcohol consumption. Risk of urinary tract morbidity was found to be positively associated with a complete lesion, number of cigarettes smoked per day and, surprisingly, physical activity. Risk of urinary tract morbidity was negatively associated with monthly alcohol consumption, a traumatic injury and the interaction between monthly alcohol consumption and a complete lesion.

Conclusion: With respect to the three morbidity outcomes in this study, cigarette smoking is the most damaging lifestyle behaviour in the spinal cordinjured population. Attention and resources should be directed towards SCI-speci”c smoking prevention and cessation programmes to prevent the development and exacerbation of chronic diseases in this unique population. Further research is needed to fully understand the associations between lifestyle and chronic diseases in the SCI population.
Characteristics of injured children attending the emergency department: patients potentially in need of rehabilitation
Authors: Sturms Leontien M , van der Sluis Corry K , Groothoff Johan W , Duis Henk Jan ten , Eisma Willem H
Published: July 2002

Objective: To provide an epidemiological overview of the characteristics of injured children and to compare hospitalized and nonhospitalized injured children to identify predictors of hospitalization and, with that, possible predictors of disablement.

Design: Retrospective analysis of data obtained from a computerized trauma registration system and medical records.

Setting: Department of Traumatology, University Hospital Groningen, the Netherlands.

Subjects: Children (0–19 years) injured in 1996 and 1997 ( n = 5057).

Results: The majority of children were injured in home and leisure accidents (53%) and sustained minor injuries. Only 55 (1%) children were severely injured (Injury Severity Score (ISS) 3 16). Overall, 512 (10%) patients required hospitalization, 19 children were referred to a rehabilitation centre, and 24 children died due to their injuries. The majority of these patients were injured in traffic. Compared with the group of nonhospitalized patients, the group of hospitalized patients consisted of more males and traffic victims, were more severely injured, and sustained more head/neck, spine, and thorax and abdomen injuries. Nonhospitalized patients incurred proportionally more upper and lower extremity injuries. The ISS, the body region of most severe injury, and injury cause (traffic accidents) were significant predictors of hospitalization.

Conclusions: Young traffic victims, severely injured children in terms of high ISS scores, and children with injuries affecting the head/neck/face or thorax/abdomen carry the highest risk of hospitalization.
The current status of bereavement follow-up in hospice and palliative care in Japan
Authors: Matsushima T , Akabayashi A , Nishitateno K
Published: July 2002

In order to explore the implementation of bereavement care in hospice/palliative care settings in Japan, a self-administered questionnaire was sent to all 54 government-approved hospice/palliative care units (PCUs) in May of 1999 (recovery rate 93%). Results showed that bereavement follow-up is performed in 37 institutes (74%) and memorial cards and services are most frequently provided. Memorial cards are provided mainly by nurses, and memorial services involve many health care professionals as well as volunteers. Religious workers tended to be involved in memorial services and social group meetings. Individually oriented interventions such as telephone contacts, personal visits and personal counselling were reportedly used less often. The need for individual-oriented programmes was recognized, and many institutes were considering the expansion of their programmes to include them. However, the difficulties of implementing such care at hospice/PCUs were also raised. Two socio-cultural factors possibly affecting bereavement care in Japan, namely, the roles of family and religious (Buddhist) ceremonies were discussed. It was pointed out that the spirit of bereavement care may be embodied in existing religious ceremonies. We conclude that it is necessary to develop bereavement care programmes based on common, basic hospice care tenets while making full use of existing local resources and taking into account regional values.
One nation, pulling apart: the basis of persistent poverty in the USA
Authors: Glasmeier Amy K.
Published: July 2002

Poverty in America has grown persistently throughout the twentieth century. Once a condition confined to immigrants, women and children, by the 1930s poverty became tied to the geographic development of the nation. Historically, poverty policy has emphasized individual moral responsibility while ignoring its geographic and structural origins. A weak attempt to address the deeper origins of poverty in the 1960s imploded with the economic crisis of the 1980s and the slide into conservative politics. By 1997 more than 700 counties in the USA were in economic distress. Few new initiatives have been offered to resolve this decades-old problem.
Dynamics of secondary airflow and sediment transport over and in the lee of transverse dunes
Authors: Walker Ian J. , Nickling William G.
Published: July 2002

Recent research literature on secondary airflow and sediment transport patterns over flow-transverse dunes is reviewed. Various issues surrounding the behaviour, modelling and sedimentological implications of near-surface airflow dynamics over dunes are discussed, including: the Law of the Wall; the Jackson and Hunt airflow model; the effects of streamline compression, acceleration and curvature on stoss slope shear stress; and, in particular, recent efforts to characterize secondary lee-side airflow patterns. A revised conceptual model of lee-side airflow is presented and areas for further research are identified regarding the implications of such patterns for dune sedimentary dynamics, morphology, and migration.
Timing, equilibrium-line altitudes and climatic implications of two early-Holocene glacier readvances during the Erdalen Event at Jostedalsbreen, western Norway
Authors: Dahl Svein Olaf , Nesje Atle , Lie Øyvind , Fjordheim Kristine , Matthews John A.
Published: July 2002

Following the Younger Dryas, the first evidence of glacial activity in southern Norway in response to climatic change occurred during the early Holocene, when terminal moraines from the Erdalen Event formed beyond the position of later ‘Little Ice Age’ moraines. In front of present outlet glaciers on both sides of the Jostedalsbreen ice cap, sets of pre-‘Little Ice Age’ marginal moraines have been morphostratigraphically corre lated with the Erdalen Event. The lithostratigraphy in a peat bog at Hellemyrane in Jostedalen, western Norway, provides firm evidence for a two-phase Erdalen Event associated with two glacier readvances of Nigardsbreen at the Preboreal/Boreal transition. Radiocarbon dates from the peat bog give age estimates for the two phases: the first Erdalen Event readvance took place between 10 100 and 10 050 cal. BP, while the second occurred close to 9700 cal. BP. The lowering of the equilibrium-line altitude (ELA) during these readvances is estimated using the ‘Little Ice Age’ ratio (LR) approach to be about 230 m and 215 m, respectively. The first readvance is attributed to an increase in winter precipitation, while the second readvance may have been primarily caused by a marked drop in summer temperature which reactivated already existing ice masses.
A mid-Holocene shift in Arctic sea-ice variability on the East Greenland Shelf
Authors: Jennings Anne E. , Knudsen Karen Luise , Hald Morten , Hansen Carsten Vigen , Andrews John T.
Published: July 2002

Records of iceberg-rafting and palaeohydrography from two East Greenland shelf cores (JM96-1206/1-GC and JM96-1207/1-GC) are reported. Benthic foraminifera, stable isotopes and IRD fluxes indicate a shift toward colder, lower-salinity ‘polar’ conditions c. 5 cal. ka. A new proxy of iceberg-rafting on the East Greenland Shelf is the flux of calcium carbonate (TIC) thought to be derived from glacial erosion of Cretaceous calcareous mudstones. A change in the regularity and spacing of carbonate flux peaks at c. 4.7 cal. ka in JM96-1207 coincides with the onset of Neoglacial cooling in the Renland ice core δ18O record. We propose that the carbonate flux peaks between 4.7 and 0.4 cal. ka are related to sea-surface coolings associated with increased flux of polar water and sea ice in the East Greenland Current. These peaks are synchronous with sea-surface coolings interpreted from North Atlantic deep-sea cores, but additional peaks centred around 2.4 and 3.8 cal. ka in JM96-1207 suggest that the shelf site captures higher-frequency events. The data indicate that severe Arctic sea-ice events began in the Neoglacial interval, and that earlier-Holocene cool events in deep-sea records are associated with other processes, such as release of meltwater from residual glacier ice and glacial lakes.
Holocene geochronology of a continentalshelf mudbelt off southwestern Africa
Authors: Meadows Michael E. , Rogers John , Lee-Thorp Julia A. , Bateman Mark D. , Dingle Richard V.
Published: July 2002

The Holocene lithostratigraphy and geochronology of sediments on an inner continental-shelf mudbelt off the west coast of southern Africa is presented. Based on a study of seven large gravity cores, numerous grab samples and two vibracores, two distinctive sections of the mudbelt have been identi” ed. The northern section is associated with the Orange River prodelta, and is dominated by laminated clay-rich sediments, while the southern section off Namaqualand is associated with more homogeneous muds. AMS radiocarbon ages of 31 samples from these cores are problematic due to the absence of expected modern material at the sedimentocean interface and numerous age reversals and inconsistencies in some of the cores. Possible mechanisms to explain the apparently anomalously old surface and near-surface samples are suggested. Most likely expla nations appear to lie in a combination of sediment-retrieval problems, the periodic loss of ” ne particulate organic carbon from within the water column, the sampling of possible relic sediments and, most likely of all, the incorporation into the sediments of 14C-depleted terrigenous organic matter. The age reversals are especially evident in the laminated sediments, and the entrainment of ‘old’ carbon from the terrestrial source of these sediments is offered as the most parsimonious explanation. Stable carbon isotope analyses and a single lumi nescence age support the contention that radiocarbon date inconsistencies are a consequence of terrestrial inputs of carbon which is non-contemporaneous with the actual time of sedimentation. In studies of offshore accumulations of terrigenous material, the marine-derived organic fraction may therefore prove a more reliable measure of radiocarbon chronology.
Fossil grass cuticles from lacustrine sediments: a review of methods applicable to the analysis of tropical African lake cores
Authors: Wooller M. J.
Published: July 2002

The need for alternatives to fossil pollen for the reconstruction of vegetation dominated by grasses has prompted the use of grass cuticles, which lack a described method of analysis. Methods used to analyse sediments for palaeoecological materials allied to grass cuticles, including microscopic charcoal, phytoliths and plant cuticles, are reviewed. A simple set of methods and protocols for extracting, identifying and quantifying fossil grass cuticles are presented.
An advance of Soler Glacier, North Patagonian Icefield, at c. AD 1222–1342
Authors: Glasser Neil F. , Hambrey Michael J. , Aniya Masamu
Published: July 2002

Soler Glacier is a temperate outlet glacier on the eastern side of the North Patagonian Icefield in Chile. The glacier is currently receding from its ‘Little Ice Age’ maximum position, attained sometime between ad 1600 and 1900. Across the snout and forefield of the glacier is an arcuate belt of well-sorted granule gravel and coarse sand containing tree remains. These sediments are interpreted as reworked glaciolacustrine material, elevated to the glacier surface by thrusting and folding. Radiocarbon dating of samples of tree remains in these reworked glaciolacustrine sediments demonstrates that the glacier overrode this lake bed sometime between ad 904 and ad 1334. In situ tree remains plastered onto a large boulder in front of the glacier constrain this advance to the period between ad 1222 and ad 1342. This advance precedes by several hundred years the maximum ‘Little Ice Age’ extent of other North Patagonian Icefield outlet glaciers, suggesting either an early age for the onset of ‘Little Ice Age’ conditions or a previously unrecognized period of glacier advance. Prior to the advance at c. ad 1222 to ad 1342, Soler Glacier was more recessed than at present, confirming the dynamic response of Patagonian glaciers to Holocene climatic fluctuations.
Detecting woodland remnants in cultural landscapes: modern pollen deposition around small woodlands in northwest Scotland
Authors: Bunting M. Jane
Published: July 2002

Modern pollen deposition in and around woodland fragments in a largely open cultural landscape in northwest Scotland is investigated using moss polsters and surface sediment samples from small lakes. The percentage of local arboreal (tree and shrub) pollen types declines rapidly with distance from the woodland edge, generally reaching background levels in less than 100 m. Even at the woodland edge or under the canopy, some samples contain less than 30% local arboreal pollen. The relationship between percentage of local arboreal pollen and distance from the woodland edge does not vary with changing topographic relationship between sample location and the woodland edge, but does differ according to the vegetation community outside the woodland. Comparison of pollen assemblages from 11 small lake basins (mean size 1.0 hectare) with assemblages from moss polsters collected near the lake edge suggests that the pollen source area for arboreal pollen types is in the order of 300 m for peat samples and over 400 m for lake sediments. Implications for interpretation of palaeorecords are considered.
Complex North Atlantic Oscillation (NAO) Index signal of historic North Atlantic storm-track changes
Authors: Dawson A. G. , Hickey K. , Holt T. , Elliott L. , Dawson S. , Foster I. D.L. , Wadhams P. , Jonsdottir I. , Wilkinson J. , McKenna J. , Davis N. R. , Smith D. E.
Published: July 2002

Previous reports have suggested a link between increased storminess in the North Atlantic during recent years with a period of time during which the North Atlantic Oscillation Index has been strongly positive. New analyses of late nineteenth-century gale-day data for meteorological stations in northern Scotland and western Ireland indicate that the relatively high storminess that characterized this period was associated with monthly NAO Index values that rarely exceeded +2 and, on several occasions, were strongly negative. It is speculated that this difference may reflect the influence of an expanded sea-ice cover in the Greenland Sea that caused a considerable southward displacement of the North Atlantic storm track during the late nineteenth century. Such changes imply that the polar atmospheric and oceanic fronts in the North Atlantic were displaced southward during the late nineteenth century.
Testicular and spermatotoxic effect of nitrate in mice
Authors: Pant N , Srivastava SP
Published: July 2002

A study was conducted with nitrate to assess the testicular and spermatotoxic effects in mice at doses to which human beings are exposed as well as at higher dose levels in the drinking water. Potassium nitrate was administered to mice at dose levels 90, 200, 500, 700 and 900 ppm for 35 days. There was no difference in the uptake of water in control and treated animals. The amount of nitrate intake// mouse///day calculated on the basis of water intake in the different groups ranged from 22.5 to 27, 50 to 60, 125 to 150, 175 to 210 and 225 to 270 mg///kg body weight. No changes were evident in the body weight, testicular, epididymal and accessory organ weight at all the dose levels tested, although a decline in sperm count and sperm motility along with an increase in abnormal sperm was noticed at 900 ppm. The activity of marker testicular enzymes, mainly 17-β hydroxysteroid dehydrogenase (17-β HSD) and figlutamyl transpeptidase (fi-GT), associated with specific cell types were altered. Histopathological changes including atrophy and disturbed spermatogenesis were observed only at the 900-ppm dose level. In conclusion, we can say that the testicular and spermatotoxic effects are observed only at the highest dose level, which is not likely to be encountered in the drinking water.
Different clinical features of amitraz poisoning in children
Authors: Atabek M Emre , Aydin K , Erkul I
Published: July 2002

Objective: To evaluate clinical experience of amitraz poisoning in children. Methods: In this study, the clinical and laboratory features of amitraz poisoning in 14 children are presented and compared with previous studies. Results: This study revealed that clinical manifestations of poisoning by oral and dermal routes appeared within 30–150 min, and that central nervous system (CNS) depression, which is the most important sign, improved within 6–24 hours and other signs within 24–72 hours. Unlike the findings in other studies, three severe cases in our study had reversible mydriasis and one of them required resuscitation because of cardiopulmonary arrest occurring as a result of serious respiratory depression. In addition, hepatic function test levels had increased in these three cases, and aspiration pneumonitis existed because of emesis in two of them. Conclusion: There is little information in the literature about dermal poisoning. The signs and symptoms of dermal poisoning were relatively mild compared with oral poisoning, and there were no topical signs. The classical signs of¬small2small-adrenergic stimulation such as marked sinusal bradycardia and mydriasis as reported in many poisoning cases of animals have not been reported before our three severe cases among children.
Why have cells selected reactive oxygen species to regulate cell signaling events?
Authors: Stadtman E R , Levine R L
Published: July 2002

There is a growing body of evidence demonstrating that exposure of cells to reactive oxygen species (ROS) leads to oxidative modification of nucleic acids, proteins, and lipids, and that such modifications can contribute to the development of a number of diseases and aging. This raises the question: If ROS are so damaging to cells, why have cells selected ROS to trigger activation of so many cell signaling pathways?
Defining hormesis: comments on Calabrese and Baldwin (2002)
Authors: Chapman P M
Published: July 2002

The definition of hormesis should not include non scientific judgments as to beneficial or harmful effects. Evaluating the significance of hormesis is a separate issue that ultimately requires risk:risk comparisons, particularly since the evolutionary basis for hormesis appears to be Lamarkian rather than Darwinian. It is arguable whether ‘hormesis’ is the correct umbrella term for all low-dose exposure responses, in particular those at higher organization levels than single species, or whether it includes arousal responses.
Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations
Authors: Burgaz S , Karahalil B , Canli Z , Terzioglu F , Ançel G , Anzion R BM , Bos R P , Hüttner E
Published: July 2002

To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p<0.05, p<0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 μg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.
Intrarectal administration of 5-aminosalicylic acid to rabbits and dogs
Authors: Berryman E L , Zerouala A C , Meschter C , Spenard J
Published: July 2002

Intrarectal administration of 5-aminosalicylic acid (5-ASA) to rabbits and dogs was performed to obtain safety data. Groups of rabbits and dogs received twice daily intrarectal doses of 250, 500 or 1000 mg 5-ASA for 14 consecutive days. Treatment had no adverse effect on the behaviour or performance of the animals and microscopic examination revealed no evidence of systemic or local toxicity.
Multi-state models for event history analysis
Authors: Andersen Per Kragh , Keiding Niels
Published: July 2002

An introduction to event history analysis via multi-state models is given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.
Estimation of covariate-dependent Markov transition probabilities from nested case-control data
Authors: Borgan Ørnulf
Published: July 2002

Multi-state models are used to describe situations where individuals may move among a finite number of states defined by specific conditions of health, including death. The transition intensities of the models are described by proportional hazards models, and it is reviewed how estimation of the regression parameters and the baseline transition intensities may be performed when only nested case-control data are available for all or some of the transitions. The regression parameter estimates and the estimates of baseline transition intensities are combined to give estimates of the integrated transition intensities for specified covariate histories, and from these estimates covariate-dependent Markov transition probabilities are derived.
Incidence of enhancement of the trigeminal nerve on MRI in patients with multiple sclerosis
Authors: van der Meijs A HC , Tan I L , Barkhof F
Published: July 2002

The purpose of this study is to review the incidence of contrast enhancement of the trigeminal nerve on magnetic resonance imaging (MRI) in a large cohort of patients with multiple sclerosis (MS). MRI scans of 851 MS patients participating in a phase III clinical trial were reviewed for the presence of gadolinium enhancement on postcontrast T1-weighted images. If enhancement was present, it was documented whether this involved only the proximal or also the distal part of the fifth nerve, and whether the abnormality was unilateral or bilateral. In 24 (2.8%) patients, enhancement of the trigeminal nerve was observed, and was bilateral in 16 (66.7%) of those. In 19 (79.2%) patients with abnormal nerves, enhancement extended to the distal part of the trigeminal nerve (into Meckel’s cave). The results of this study indicate a high, probably clinically silent, incidence of trigeminal nerve demyelination in MS and frequent involvement of the peripheral type of myelin in MS.
Results of an international questionnaire on immunosuppressive treatment of multiple sclerosis
Authors: Hommes O R , Weiner H L
Published: July 2002

In November 2000, a questionnaire was sent to 702 multiple sclerosis (MS) centers. Data on the institute, treating neurologists, number of MS patients under care, and the number of patients treated with immunosuppressive treatments were collected. The results indicate that overall, around 10% of MS patients are treated with one of four drugs: azathioprine, cyclophosphamide, methotrexate, and mitoxantrone. Azathioprine was most frequently used. More than 30% of MS patients in France are treated with immunosuppressive drugs. In some other countries, these treatments are hardly prescribed.
The Luminance Differences index: a new indicator of user preferences in daylit spaces
Authors: Parpairi K , Baker NV , Steemers KA , Compagnon R
Published: July 2002

This paper presents part of the findings of a research project conducted at the Martin Centre University of Cambridge, which looked into how daylighting quality affects the users of a library interior. It discusses the importance of luminance in the field of view for the perception of quality and introduces a new index named Luminance Differences (LD) which represents luminance variability (‘noise’). It will be illustrated that this index was successful in relating to the users’ subjective assessments of daylight quality, suggesting that it can be used to predict user preferences in a daylit space.
Adjuvant Therapy for Breast Cancer: Practice Patterns of Community Physicians
Authors: Harlan Linda C. , Abrams Jeffrey , Warren Joan L. , Clegg Lin , Stevens Jennifer , Ballard-Barbash Rachel
Published: July 2002

PURPOSE: We evaluated the use of adjuvant therapy for breast cancer using the National Institutes of Health (NIH) Consensus Development Conference statements as guideposts for assessing how rapidly community physicians adopt recommended therapies.

PATIENTS AND METHODS: Women with stage I through IIIA breast cancer diagnosed in 1987 through 1991 and in 1995 were randomly sampled from the population-based National Cancer Institute Surveillance, Epidemiology, and End-Results program. A total of 8,106 women were included in the study with younger women, ≤ 50 years, being oversampled. Their treating physicians were asked to verify whether chemotherapy, hormonal therapy, or both were given.

RESULTS: After adjusting for clinical and nonclinical factors, the use of 1985 recommendations for adjuvant therapy in women with node-positive disease was already high at 80% in 1987 and increased slightly to 84% by 1995. Use of combined multidrug chemotherapy plus tamoxifen increased. In contrast, the use of 1990 recommendations for adjuvant therapy for node-negative disease was slightly less than 13% in 1987 and increased markedly to 57% by 1995. For women with node-negative tumors ≥ 1 cm in size diagnosed in 1995, 40% received tamoxifen, 16% combination chemotherapy, and 7% both, an increase from 10%, 5%, and 0.4%, respectively, in 1987.

CONCLUSION: Community physicians began prescribing adjuvant chemotherapy and hormonal therapy in advance of publication of the NIH consensus statement in 1990. Adoption of recommended treatments for node-negative disease has been less complete compared with node-positive tumors, perhaps reflecting the more complex nature of the clinical trials data or the smaller anticipated benefit from adjuvant therapy for this disease subset.
Psychiatric Morbidity and Impact on Hospital Length of Stay Among Hematologic Cancer Patients Receiving Stem-Cell Transplantation
Authors: Prieto Jesús M. , Blanch Jordi , Atala Jorge , Carreras Enric , Rovira Montserrat , Cirera Esteve , Gastó Cristóbal
Published: July 2002

PURPOSE: To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation (SCT) and to estimate their impact on hospital length of stay (LOS).

PATIENTS AND METHODS: In a prospective inpatient study conducted from July 1994 to August 1997, 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution. Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death, yielding a total of 1,062 psychiatric interviews performed. Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Univariate and multivariate linear regression analyses were used to identify variables associated with LOS.

RESULTS: Overall psychiatric disorder prevalence was 44.1%; an adjustment disorder was diagnosed in 22.7% of patients, a mood disorder in 14.1%, an anxiety disorder in 8.2%, and delirium in 7.3%. After adjusting for admission and in-hospital risk factors, diagnosis of any mood, anxiety, or adjustment disorder (P = .022), chronic myelogenous leukemia (P = .003), Karnofsky performance score less than 90 at hospital admission (P = .025), and higher regimen-related toxicity (P < .001) were associated with a longer LOS. Acute lymphoblastic leukemia (P = .009), non-Hodgkin’s lymphoma (P = .04), use of peripheral-blood stem cells (P < .001), second year of study (P < .001), and third year of study (P < .001) were associated with a shorter LOS.

CONCLUSION: Our data indicate high psychiatric morbidity and an association with longer LOS, underscoring the need for early recognition and effective treatment.
Phase II Study of Paclitaxel Plus Gemcitabine in Refractory Germ Cell Tumors (E9897): A Trial of the Eastern Cooperative Oncology Group
Authors: Hinton Stuart , Catalano Paul , Einhorn Lawrence H. , Loehrer Patrick J. , Kuzel Timothy , Vaughn David , Wilding George
Published: July 2002

PURPOSE: Despite great success in the treatment of disseminated germ cell tumors, 20% of patients are incurable and become candidates for investigational therapy. Paclitaxel and gemcitabine have shown activity as single agents in refractory germ cell tumors and can be combined with manageable toxicity.

PATIENTS AND METHODS: Patients with germ cell tumors believed to be incurable with chemotherapy or surgery were treated with paclitaxel 110 mg/m2 and gemcitabine 1,000 mg/m2 intravenously on days 1, 8, and 15 of a 4-week cycle for a maximum of six cycles. Patients were evaluated for response and toxicity.

RESULTS: Twenty-eight of 30 enrolled patients were assessable. Toxicity was primarily hematologic but was manageable with only a single case of neutropenic fever. Six (21.4%) of 28 patients responded, including three complete responses. Two of the complete responders were continuously disease-free at 15+ and 25+ months.

CONCLUSION: Paclitaxel plus gemcitabine is an active regimen in refractory germ cell tumors, with an acceptable toxicity profile. This regimen has the possibility for long-term disease-free survival in this refractory patient population.
Oncologists’ Attitudes Toward and Practices in Giving Bad News: An Exploratory Study
Authors: Baile Walter F. , Lenzi Renato , Parker Patricia A. , Buckman Robert , Cohen Lorenzo
Published: July 2002

PURPOSE: To examine the attitudes and practices of oncologists in disclosure of unfavorable medical information to cancer patients.

METHODS: A questionnaire was administered to a group of physicians who attended the 1999 Annual Meeting of the American Society of Clinical Oncology. The questionnaire assessed demographic and practice-related information and the frequency of patient encounters in which unfavorable cancer-related information was disclosed. Participants were also asked about difficulties they had when approaching stressful discussions and communication strategies used in giving unfavorable information.

RESULTS: The questionnaire was completed by 167 oncologists. Sixty-four percent were medical oncologists. Thirty-eight percent practiced in North America, 26% practiced in Europe, 13% practiced in South America, and 13% practiced in Asia. Participants gave bad news to patients an average of 35 times per month. Discussing no further curative treatment and hospice was reported as most difficult. In disclosing the cancer diagnosis and prognosis, physicians from Western countries were less likely to withhold unfavorable information from the patient at the family’s request, avoid the discussion entirely, use euphemisms, and give treatments known not to be effective so as not to destroy hope than physicians from other countries. There was significant variability in opinions regarding the best time to discuss resuscitation, with 18% of respondents believing that it should be done close to the end of life.

CONCLUSION: There was significant variability in how physicians approach information disclosure to cancer patients. Factors such as geographical region and cultural and family variables may be important influences in this process.