bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Myeloid Leukemia Stem Cells
Authors: Jamieson Catriona H. 
Published: December 2008

AbstractChronic myeloid leukemia (CML) is typified by robust marrow and extramedullary myeloid cell production. In the absence of therapy or sometimes despite it, CML has a propensity to progress from a relatively well tolerated chronic phase to an almost uniformly fatal blast crisis phase. The discovery of the Philadelphia chromosome followed by identification of its BCR-ABL fusion gene product and the resultant constitutively active P210 BCR-ABL tyrosine kinase, prompted the unraveling of the molecular pathogenesis of CML. Ground-breaking research demonstrating that BCR-ABL was necessary and sufficient to initiate chronic phase CML provided the rationale for targeted therapy. However, regardless of greatly reduced mortality rates with BCR-ABL targeted therapy, most patients harbor quiescent CML stem cells that may be a reservoir for disease progression to blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, only recently have the HSC and progenitor cell–specific effects of the molecular mutations that drive CML been investigated. This has provided the impetus for investigating the genetic and epigenetic events governing HSC and progenitor cell resistance to therapy and their role in disease progression. Accumulating evidence suggests that the acquired BCR-ABL mutation initiates chronic phase CML and results in aberrant stem cell differentiation and survival. This eventually leads to the production of an expanded progenitor population that aberrantly acquires self-renewal capacity resulting in leukemia stem cell (LSC) generation and blast crisis transformation. Therapeutic recalcitrance of blast crisis CML provides the rationale for targeting the molecular pathways that drive aberrant progenitor differentiation, survival and self-renewal earlier in disease before LSC predominate.
New Agents in the Treatment of CLL
Authors: O’Brien Susan 
Published: December 2008

AbstractChemoimmunotherapy has resulted in high complete remission rates and long remission duration in patients with chronic lymphocytic leukemia (CLL) but relapses occur and curative strategies still need to be developed. A wealth of new agents with a wide variety of mechanisms of action against CLL are currently in clinical trials. Twelve of these agents, which are in various stages of development varying from Phase I to Phase III trials, will be discussed. These include alkylating agents, monoclonal antibodies, immune modulators, cyclin-dependent kinase (CDK) inhibitors, BCL-2 family member inhibitors, protein kinase C (PKC) inhibitors, SRC inhibitors, HSP-90 inhibitors and small modular immune pharmaceutics (SMIP).
Pain Management in Sickle Cell Disease: Palliative Care Begins at Birth?
Authors: Benjamin Lennette 
Published: December 2008

Abstract
People with sickle cell disease (SCD) are living longer, but their lives are impacted even more by the unpredictable intermittent or constant pain that is often poorly managed over a lifetime. To address this problem, an interdisciplinary team approach is needed that brings the medical professionals together for optimal compassionate care that is coordinated from the beginning of life and throughout the patient’s lifespan.The hematologist, whenever possible, should take the lead. Effective models that have been developed to address SCD pain, such as the Day Hospital, The Recidivism Project and various Home Care models, need to be integrated into an overarching plan on a continuum with an underpinning philosophy that will sustain such a program. While the focus of palliative care has been end of life, its philosophies fit the chronic disease model and support an integrated team approach to the SCD pain management dilemma. The patient-focused and family-oriented interventions can be modeled to fit “any place, any time,” outpatient, inpatient or the home, with homecare and other support systems. Such are the needs in SCD: appropriate, timely and compassionate care to prevent or relieve suffering and to preserve dignity, meaning, value and quality of life with improvement that is translational from birth until the end of life.
Determinants of career aspirations of medical students in southern China
Authors: She LingBing , Wu BingLi , Xu LiYan , Wu JianYi , Zhang PiXian , Li EnMin 
Published: December 2008

AbstractBackgroundWith recent changes in both the Chinese medical system and compensation of medical doctors, the career aspirations of Chinese medical students have become more diverse. Shantou University Medical College has conducted evaluations and instituted programs to enhance student preparedness to enter a variety of medical careers.MethodsA survey was conducted with 85 students to evaluate medical career aspirations and their association with family background, personal skills, English language proficiency, and interest in biomedical research, which were considered as possible factors affecting their career interest.ResultsChinese students aspire to traditional as well as nontraditional medical careers. A significant minority of students are now interested in nontraditional careers such as medical teaching or research. However, poor proficiency in the English language and lack of computer skills may limit their academic and career opportunities.ConclusionCareer aspirations have changed among medical undergraduates. Although many wish to pursue a traditional clinical doctor career, many are interested in research and teaching careers. Factors such as family background, personal characteristics, school mentoring, and extracurricular support may play a role.
The Influence of Instrumented Striker Configuration on the Results of Dynamic Toughness Testing
Authors: Lucon Enrico 
Published: December 2008

Abstract
Several studies are available on the influence of the edge radius of instrumented strikers (ASTM — 8 mm or ISO — 2 mm) on the results of both non-instrumented and instrumented Charpy tests. This paper investigates the effect of using either a 2 mm or a 8 mm striker when performing dynamic toughness tests at impact loading rates on precracked Charpy specimens. Existing data from tests run in the ductile-to-brittle region (dynamic Master Curve reference temperature) and in the upper shelf regime (ductile initiation fracture toughness and crack resistance curves) have been analyzed. The results show that 2 mm strikers tend to yield lower cleavage fracture toughness in the transition region (although the effect cannot be considered statistically significant), whereas the influence of striker configuration is negligible in the upper shelf regime when data are generated using the low-blow multiple-specimen technique.
Potential Network Mechanisms Mediating Electroencephalographic Beta Rhythm Changes during Propofol-Induced Paradoxical Excitation
Authors: McCarthy Michelle M. , Brown Emery N. , Kopell Nancy 
Published: December 2008

Propofol, like most general anesthetic drugs, can induce both behavioral and electroencephalographic (EEG) manifestations of excitation, rather than sedation, at low doses. Neuronal excitation is unexpected in the presence of this GABAA-potentiating drug. We construct a series of network models to understand this paradox. Individual neurons have ion channel conductances with Hodgkin–Huxley-type formulations. Propofol increases the maximal conductance and time constant of decay of the synaptic GABAAcurrent. Networks range in size from 2 to 230 neurons. Population output is measured as a function of pyramidal cell activity, with the electroencephalogram approximated by the sum of population AMPA activity between pyramidal cells.These model networks suggest propofol-induced paradoxical excitation may result from a membrane level interaction between the GABAAcurrent and an intrinsic membrane slow potassium current (M-current). This membrane level interaction has consequences at the level of multicellular networks enabling a switch from baseline interneuron synchrony to propofol-induced interneuron antisynchrony. Large network models reproduce the clinical EEG changes characteristic of propofol-induced paradoxical excitation. The EEG changes coincide with the emergence of antisynchronous interneuron clusters in the model networks. Our findings suggest interneuron antisynchrony as a potential network mechanism underlying the generation of propofol-induced paradoxical excitation. As correlates of behavioral phenomenology, these networks may refine our understanding of the specific behavioral states associated with general anesthesia.
Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?
Authors: Rotondi Mario , Leporati Paola , La Manna Antonella , Pirali Barbara , Mondello Teresa , Fonte Rodolfo , Magri Flavia , Chiovato Luca 
Published: December 2008

ObjectiveMorbid obesity (body mass index (BMI)≥40 kg/m2) is associated with thyroid function disturbances, with a high rate of subclinical hypothyroidism (SH) being the most consistently reported. We evaluated the circulating thyroid function parameters in morbid obese patients and related the results to the presence of circulating thyroid antibodies (Thyr-Ab).Design and methodsMorbid obese patients were consecutively enrolled (n=350). Two control groups were used: control group (CG)1, healthy normo-weight subjects (n=50); CG2, normo-weight patients with SH (n=56) matched for TSH with the obese patients with SH. Serum levels of free triiodothyronine (FT3), free thyroxine (FT4), TSH, antithyroglobulin antibodies, and antithyroperoxidase antibodies were measured in all patients.Resultsi) Compared with CG1, obese patients having thyroid function parameters in the normal range and negative Thyr-Ab showed significantly higher serum TSH and lower free thyroid hormones levels, but a similar FT4/FT3 ratio; ii) SH was recorded in 13.7% obese patients; iii) compared with CG2, obese patients with untreated SH had a significantly lower rate of positive Thyr-Ab (32.1 vs 66.1%; P<0.005); iv) no gender prevalence was observed in SH obese patients with negative Thyr-Ab; and v) the comparison of the untreated SH patients (obese and normo-weight) with CG1 demonstrated that in SH obese subjects, unlike normo-weight SH patients, the FT3 levels were significantly lower. This resulted in a normal FT4/FT3 ratio in SH obese patients.ConclusionThyroid autoimmunity is not a major cause sustaining the high rate of SH in morbid obese patients. In these patients, the diagnosis of SH itself, as assessed by a raised TSH alone, appears questionable.
Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four Italian kindreds with familial hypocalciuric hypercalcemia
Authors: Cetani Filomena , Lemmi Monica , Cervia Davide , Borsari Simona , Cianferotti Luisella , Pardi Elena , Ambrogini Elena , Banti Chiara , Brown Edward M , Bagnoli Paola , Pinchera Aldo , Marcocci Claudio 
Published: December 2008

ObjectiveIdentification and characterization of calcium-sensing receptor (CASR) mutations in four unrelated Italian kindreds with familial hypocalciuric hypercalcemia.DesignClinical evaluation and genetic analysis ofCASRgene. Functional characterization of mutatedCASRs.MethodsDirect sequencing ofCASRgene in genomic DNA. Studies ofCASR-mediated increases in cytosolic calcium concentration [Ca2+]iinCASR-transfected COS-7 cellsin vitro.ResultsFour unreported heterozygousCASRmutations were identified, including three missense (H595Y, P748H, and C765W) and one splice site (IVS2+1G>C) mutation. The H595Y, P748H, and C765W mutant receptors, although expressed at normal levels on the cell surface, showed a reduced response in [Ca2+]irelative to the wildtype (WT)CASRto increasing extracellular calcium concentrations. Cotransfection experiments showed that the H595Y and P748H mutants did not affect the apparent affinity of the WTCASRfor calcium, suggesting that they do not exert a dominant-negative effect. On the other hand, the co-transfected C765W mutant decreased the maximum response of the WTCASRto calcium, suggesting that it may reduce the effective concentration of the normalCASRon the cell surface or impair its maximal signaling capacity.ConclusionsFourCASRmutations were identified. The reduced functional responses to extracellular calcium and normal expression of the mutant receptors suggest that conformational changes account for alteredCASRactivity. Moreover, a reduced complement of normalCASRsin these heterozygous patients, perhaps combined with a mutant receptor-induced decrease in maximal activity of the WT receptor, may contribute to defective calcium-sensingin vivo.
VARIABILITY IN THE RESPONSE OF THE SYMPHYSIS PUBIS OF THE GUINEA-PIG TO RELAXIN
Authors: TALMAGE R. V. , HURST W. R. 
Published: December 2008

A revised method of assay for relaxin is described, based on a combination of the previously used palpation method and a procedure in which the increase in interpubic distance caused by relaxin is recorded by X-raying the guinea-pig before and 6 hr. after the administration of relaxin. A guinea-pig X-ray unit has been defined as that amount of relaxin which when given to fifty animals will cause an average symphysial spread of 0·35 mm. within 6 hr., the animals being held down when X-rayed by 500 g. weights on the rear legs.
A critical examination of the response of the guinea-pig pubic symphysis to relaxin has been made, and the high degree of variability has been statistically analysed and discussed.
PREGNANCY IN INSULIN-TREATED ALLOXAN DIABETIC RATS
Authors: FERRET P. , LINDAN O. , MORGANS MARGARET E. 
Published: December 2008

1. The fertility and outcome of pregnancy have been studied in alloxan diabetic rats treated with insulin. The diabetes was only partly controlled, but the general condition of the diabetic mothers was good.
2. Fertility rate was increased compared with that in animals in which the diabetes was not treated with insulin. Stillbirth rate and neonatal death rate (5% combined loss) and the percentage of weaned animals (89%) were normal, as contrasted with a 37% combined stillbirth and neonatal mortality rate and 50% death-rate before weaning in the offspring of untreated diabetic mothers.
3. It is concluded that alloxan diabetes does not adversely affect the foetal mortality, neonatal death-rate or the feeding of young animals unless it impairs the general health of the mother.
ASSAY OF DIABETOGENIC PITUITARY PREPARATIONS
Authors: REID E. 
Published: December 2008

1. Procedures are described for the approximate assessment, in the intact cat, of the diabetogenic potency of growth hormone preparations from ox anterior-pituitary glands (section A).
2. Partially depancreatized rats (three strains) and alloxan-diabetic rats (two strains) were insufficiently sensitive to such preparations to be of use as test animals (section B).
THE QUALITATIVE ANALYSIS OF URINARY PHENOLS AND OESTROGENS
Authors: BOSCOTT R. J. 
Published: December 2008

Typical urinary phenols and oestrogens have been converted into azo dyes by coupling with diazotized I.C.I. M5091.
The dyes have been characterized from the following data:
(a) partition properties;
(b) solubility properties in a phosphate buffer;
(c) adsorption properties;
(d) absorption spectra data 310–600 mμ.
Decalso, after treatment with barium acetate solution, has been introduced as a new adsorbent in chromatography.
The removal of indigoid pigments from urinary oestriol fractions by a new procedure is described.
The addition of thiourea and benzene to urines during acid hydrolysis affords some protection to oestradiol-3:17α.
THE ANTERIOR LOBE OF THE CATTLE PITUITARY
Authors: BASSETT E. G. 
Published: December 2008

A histological examination has been made of the anterior lobe of the pituitaries from forty-five female and fifteen male cattle classified into groups according to reproductive condition.
Differential counts for the two main secretory cell types have been made on sections at three levels and values for each group compared by analysis of variance.
Statistical treatment of results has shown that the method in which cell counts are made on one, or at the most two representative sections only from each of a number of glands is sufficiently accurate for comparative investigations, covering groups of cattle.
Only one type of acidophil cell was observed, but both 'strong' and 'weak' basophils were found. 'Strong' basophils appeared to be more frequent in glands from pregnant and stilboestrol-treated cows but were virtually absent in those from steers.
A significant difference has been found in the numbers of acidophil cells, between pituitaries from cows with normal ovaries and from those with ovarian follicular cysts.
In the first trimester of pregnancy the number of basophils was significantly higher than in normal non-pregnant cows. The relative numbers of these two cell types in pituitaries from cows treated with large doses of stilboestrol were comparable with those in pregnant cows.
There was a significantly greater acidophil number for both bulls and steers than for any of the cows. The basophil number for steers was significantly less than that for bulls or cows.
THE MODIFICATION OF LACTATION IN THE ALBINO RAT BY ENVIRONMENTAL FACTORS
Authors: EAYRS J. T. 
Published: December 2008

The growth and food consumption of mature female rats and of lactating rats and their litters reared under various conditions of illumination have been measured.
Mature female rats grew less when kept in the dark than in the light.
Newborn rats reared in total darkness by does which were allowed in the light for only 1½ hr. daily grew less during the first 18 days of life than their litter-mate controls.
Newborn rats reared under natural lighting by does with both eyes removed did not grow as well as litter-mates reared by does with one eye removed.
The mean weight of food eaten daily by mature female rats when in the dark did not differ significantly from that eaten when in natural lighting. Lactating does and their litters confined in total darkness and bilaterally enucleated does ate significantly less food than their controls. The reduction in food intake was apparent by the third day after parturition. On the other hand, when the doe received 1½ hr. illumination daily, the daily food intake of the experimental litters was depressed only during the latter part of lactation.
The discussion suggests a possible way in which the effects of darkness on the normal adult female rat and on the lactating rat may be interrelated.
ESTIMATION OF CORTICOSTEROID-LIKE SUBSTANCES IN HUMAN URINE
Authors: ROBINSON ALICE M. , NORTON JACQUELINE M. 
Published: December 2008

A technique for the extraction of urinary corticosteroids and their estimation by copper reduction is described.
Results of the application of this technique to the determination of corticosteroid excretion in normal and diseased subjects are given.
The method may be of value in clinical investigations in revealing gross abnormality in the excretion of corticosteroids.
STUDIES OF THE HUMAN THYROID FUNCTION, MEASURED BY RADIO-IODINE, AND ITS RELATION TO THE BASAL METABOLIC RATE
Authors: REISS M. , HAIGH C. P. , HEMPHILL R. E. , MAGGS R. , REISS JEAN M. , SMITH S. 
Published: December 2008

A method of estimating thyroid function with carrier-free radio-iodine which provides an arbitrary numerical scale of thyroid activity is described. It is suitable for investigating borderline thyroid dysfunction.
The results on over 500 psychiatric patients are given in the form of histograms, and arbitrary limits of normality are defined on the basis of these results.
While there is usually a correlation between the tracer method and the basal metabolic rate, cases exist in which increased thyroid activity, determined by the radio-active method, is associated with normal or subnormal b.m.r. and vice versa. This is explained as a disturbance of the sensitivity of body tissues to thyroid hormone.
The significance of under-sensitivity to thyroid hormone and related problems is discussed, and the importance of considering peripheral sensitivity of the tissues of the body in evaluating an abnormal thyroid activity is emphasized.
DIABETOGENIC ACTIVITY AS AN INHERENT PROPERTY OF GROWTH HORMONE
Authors: REID E. 
Published: December 2008

The ratio of diabetogenic activity (in the cat) to growth-promoting activity (in the rat) of growth hormone (GH) preparations obtained by various purification procedures is constant within the limits of experimental error.
Purified GH preparations were partially inactivated in a variety of ways, and the products assayed for diabetogenic and for growth-promoting activity. It appeared that the two activities were lost to the same degree.
The biological activity of the GH molecule appears to depend on the integrity of the ε-amino groups (lysine), but not on that of the α-amino groups (alanine and phenylalanine).
THE EFFECT OF ADRENALINE ON THE CELL CONTENT OF BLOOD AND SALIVA OF NORMAL MAN
Authors: GHADIALLY F. N. 
Published: December 2008

The effect of a single dose of 1 ml. 1:1000 adrenaline hydrochloride on the peripheral blood picture of fourteen normal human subjects was studied and an erythrocytosis and leucocytosis was seen in all the subjects. The magnitude of the variations observed have been recorded. No increase in the percentage of reticulocytes or a left shift in the granulocytes was noted.
As the size of the post-adrenaline erythrocytosis and leucocytosis did not diminish in four splenectomized subjects, it is suggested that splenic contraction is not the causal factor of these phenomena in man.
It seems that the post-adrenaline erythrocytosis in man is due to haemoconcentration, the granulocytosis to a mobilization of cells from the bone marrow and the lymphocytosis to a mobilization of cells from the lymph nodes and other lymphoid tissues in the body.
The variations in the salivary leucocytes after adrenaline show that, when the effect of the drug begins to wear off and the blood leucocyte level begins to fall, leucocytes are eliminated in the saliva.
When repeated injections of adrenaline were given to two normal subjects the magnitude of the lymphocytosis was no greater than after a single injection; on the other hand, a very large cumulative granulocytosis occurred, but no left shift was detected. It is suggested that the difference is probably due to the different rates of elimination and/or destruction of these cells in the body.
THE ROLE OF THE NEUROHYPOPHYSIS IN THE MILK-EJECTION REFLEX
Authors: CROSS B. A. , HARRIS G. W. 
Published: December 2008

1. Nursing and suckling behaviour of rabbits is described, and evidence given that an active process of milk ejection ('let-down') occurs in this as in other species.
2. Intravenous injection of posterior pituitary extracts in anaesthetized rabbits resulted in ejection of milk from a cannulated teat duct. The threshold dose was about 5 mU. and maximal responses were produced by 200 mU. of extract. Whole posterior pituitary extract was more effective than the oxytocic fraction, which was in turn more effective than the vasopressor fraction.
3. Stimulation of the supraopticohypophysial (s.o.h.) tract in anaesthetized rabbits also resulted in ejection of milk from a cannulated duct. Kymographic records of this response were similar to those obtained after injection of appropriate doses of posterior pituitary extract.
4. Lesions in the s.o.h. tract in lactating rabbits caused a marked diminution in the quantity of milk obtained by their litters in standard suckling tests, and incomplete evacuation of the mammary glands. Intravenous injection of posterior pituitary extract (30–200 mU.) into the does immediately before nursing gave a marked increase in the amount of milk obtained by the young and complete evacuation of the mammary glands. Stimulation of the region of the s.o.h. tract in these animals failed to elicit milk ejection from cannulated teat ducts.
5. Rabbits with hypothalamic lesions that did not involve the s.o.h. tract showed a normal milk-ejection reflex when suckled by their young, and a milk-ejection response after electrical stimulation of the s.o.h. tract.