bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of the Pianoforte on Musical Progress
Authors: Fielden Thomas
Published: January 2007

The history of music must necessarily be the history of musical performance. The earliest effort at making any musical sound must have been that of the voice, and the progress of music through its various stages is the evolution of sound from singing in single voices or unison or octaves, passing through the organum and diatessaron stages to the polyphony of the modal period, illustrating the progress from individual to combined vocal music-making: this represents the actual music-making by the purely human element. Inevitably, with the use of rhythm, possibly beginning with a form of dancing to the accompaniment of some percussion instrument, mechanical instruments, by which I mean instruments needing physical skill to play them, were evolved from the primitive psalteries and sackbuts to the modern instruments of the orchestra. In all music-making there was a need for a unifying instrument, something which one person could manipulate which would bind together a body of musicians and be as it were a means of reference in the matter of pitch and rhythm. We have little information concerning the great music-makings of old of which we read in the Old Testament—the great song of Deborah and Barak and the thanksgiving songs of David and his followers, for instance—and we do not know whether they had conductors or not; but we do know that they had psalteries and sackbuts and cymbals.
On the Nature of Musical Talent
Authors: Lowery H.
Published: January 2007

One of the outstanding applications of psychology to education during recent years has consisted in the development of methods of measuring intelligence and the results have been so successful that intelligence tests now form part of the normal procedure in selecting pupils in school for higher forms of educational training. If intelligence tests had no other value, their use would be justified in that they have enabled us to find out many facts regarding the nature of intelligence; for example, we now know that “The observed facts indicate that all branches of intellectual activity have in common one fundamental function (or groups of functions) whereas the remaining or specific elements seem in every case to be different from that in all the others.” (Spearman.) Now it is well known that aesthetic abilities are generally regarded as standing quite apart from say ordinary vocational aptitudes. The musician and the artist have often been treated by educationists as being a class by themselves, an attitude which has been fostered by the musicians who have let the idea become current that their subject is not capable of being assessed in the same terms as those of the other school subjects. This is amusingly illustrated by the case of the musical adviser to a certain education authority who refused to attend schools at the same time as the inspectors of the ordinary school subjects.
A Postscript to Mr. Grosbayne's Paper
Authors: Carse Adam
Published: January 2007

Mr. Grosbayne's most interesting paper surveys the field of conducting-literature most comprehensively. Most of the important works on the subject are named, but he also includes a large number of books which are only remotely connected with what we now understand as conducting.
On Some of the Underlying Principles of Structure in Musical Composition
Authors: Banister H. C.
Published: January 2007

My subject may seem, in title at least, technical and formal rather than aesthetic: having to do more with that which is outlined and made than with that which is inwrought and felt; with body and shape rather than with spirit and essence. So sorry, however, should I be for it to be thought that I approach the consideration of the beautiful art which we all love, in any of its richly varied aspects, with the spirit of a pedant, or as seeming to countenance the notion that music may be made or constructed merely, without being felt or inspired, that I must at the outset, as the truest introduction to the specialties of my subject, as well as to place myself right with the art and with my audience, say emphatically that, in proposing to myself to deal with some of the underlying principles of structure in musical composition, I wish to speak of structure as the expression of definite thought; as the result of that thought; as having to do with the form that the thought assumes, rather than with the shape or mould into which it is cast. Architecture has been termed “the poetry of mathematics”: that would not be said of building, which is not the expression of a poetical thought at all. So with music, the poetry of sound—or rather, perhaps, poetical feeling expressing itself through sound: the very form that it assumes is the resultant expression of the thought.
The Principles of Musical Criticism
Authors: Stainer John
Published: January 2007

The subject on which I am to address you to-day is so wide that it would be impossible to do more than to give a very brief sketch of the whole, or to enter with some minuteness into the details of a special branch. I propose to take the latter course, and, in order to clear the ground before us, I will begin by stating what I do not propose to touch upon.
Treatment of Ground
Authors: Allt Wilfrid Greenhouse
Published: January 2007

Although the modern conception of ground-bass did not emerge until the seventeenth century, its historical antecedents are not only in themselves of considerable importance and interest but vital to any comprehensive review of the subject of this paper.
The Tonality of Woodwind Instruments
Authors: Halfpenny Eric
Published: January 2007

Anyone who has studied the subject must be aware of the lack of consistency with which the principle of lateral fingerholes in wind instruments is occasionally treated in textbooks and elsewhere.
Charles Villiers Stanford (1852–1924): An Address at His Centenary
Authors: Howells Herbert
Published: January 2007

Charles Villiers Stanford belongs to history.

He died on 29 March, 1924, a voluntary exile from his native country. For Dublin, city of bis birth, had what proved almost its last sight of him in 1870. It was the year in which he exchanged the Liffey for the Cam. Thereafter he crossed and re-crossed the Narrow Seas, searching the continent for stimuli his native city, for all its fantastically brilliant wit and fascinating society, could not provide.
The Cultivation of Church Music
Authors: Monk W. H.
Published: January 2007

Two accidents in combination must form my excuse for the present attempt to address you on so important a subject as Church Music. I was asked to read a similar paper at the recent session of the Church Congress at Newcastle. After my return in the middle of October, and while my mind was still occupied with the subject, our worthy Secretary inquired whether I could occupy a blank unexpectedly occurring in his arrangement of papers for the Musical Association. With great diffidence I inquired whether he thought an afternoon might be thus occupied, and he was good enough to say it was a “grand subject,” and would be acceptable. But I must disclaim any intention of going into any one of the practical parts of the subject, since to do so within an hour's compass, in a way worthy of this Association and of my audience, would be simply impossible. What I really wish to do is to put before you certain facts as regards the “Cultivation of Church Music” in England, with a proposal for a distinct step in advance, which I trust you may be disposed to encourage.
Alessandro Stradella
Authors: Allam Edward
Published: January 2007

The legendary life of Stradella has been the subject of eight nineteenth-century operas and of at least one novel. The earliest full biographical notice of him is to be found in Bourdelot's Histoire de la musique et de ses effets (Paris 1715) and as this account, which contains the story of how Stradella's music softened the hearts of assassins, has been followed closely by Burney, Hawkins and many others, there is no need to repeat it here.
The Evolution of Twelve-Note Music
Authors: Neighbour Oliver
Published: January 2007

There has been a tendency to treat twelve-note music as an isolated phenomenon. This is appropriate in a close study of its structural features and musical purpose, but we shall be in a better position to ask the right questions about its origin and influence if we take into account other music which shows parallel developments. Such a preliminary enquiry may affect our view of its nature and historical significance, and my subject is this first step: less the evolution of twelve-note music than its place in the general evolution of music at about the time of its emergence.
Some English Contemporaries of Dunstable
Authors: Trowell Brian
Published: January 2007

Historians of English music have always found it rather tiresome that so much of their source material for the first half of the fifteenth century survives only in foreign manuscripts, and chiefly in the libraries of North Italy. Very little of this music was available, at any rate in practical editions, until two years ago, whenMusica Britannicadevoted a volume to the works of John Dunstable; and it is only recently that modern techniques of photography have made these sources abroad accessible to the scholar or editor who lacks the time or the resources to travel. As a result, this very important music has been neglected by historians and performers alike. In the most recent general history of English music, for example, the achievements of Dunstable and his contemporaries are given a mere sixteen pages out of four hundred, though at no time before or since has English music been so famous and so influential abroad. Circumstances are to blame; but it is now high time that this music should be given its due, and there are encouraging signs that such a revival will shortly come about.
The Foundations of Musical Aesthetics
Authors: Howes Frank
Published: January 2007

The last time we had any discussion of aesthetics in our Association was in 1945, when I read a paper written by Dr. Glen Haydon, which related art to theory of knowledge. This intellectual line is favoured by American philosophers. Susanne Langer, a pupil of Whitehead, has in her Philosophy in a New Key (1942) used not so much art in general as music in particular as the key to her theory of knowledge, which is a semantic theory like Glen Haydon's. This trend is worth noting and contrasting with theories of musical aesthetics in which emotion is the kernel. Among musicians it is almost axiomatic that the stock-in-trade in which they deal is feeling in the medium of sound. They apply their technique to sound production in order to do a deal with their audiences in feeling. One of the fundamental problems of the aesthetics of music is therefore to examine this presupposition.
Concert Life in Eighteenth Century England
Authors: Sadie Stanley
Published: January 2007

The Period following Purcell's death has long been looked upon as one of the Dark Ages of English music. It is unquestionably true that Britain took a long time to produce her next really great composer, but our readiness to accept a musical back seat and our refusal to make unjustifiable claims on behalf of British music have tended to blind us to the true facts of the musical life of eighteenth-century England. The fact that Handel prospered here, that Haydn wrote some of his finest music for London audiences, and that whole hosts of minor masters settled here—J. C. Bach and Geminiani, for example—surely tells us a good deal about the standards of taste pertaining among London audiences. In fact, concert life in eighteenth-century England as a whole had a variety and vitality to which it would be hard to find a parallel. Not only were concerts held in the fashionable London salons, but in the ‘Great Rooms’ of taverns in villages which today are barely large enough to find a place on a map.
The English Anthem 1580—1640
Authors: Le Huray Peter
Published: January 2007

During the past forty years much of the finest pre-Restoration service music has come back into the cathedral repertoire. So many are the distinguished scholars who have contributed to this welcome revival that one hesitates to single out any by name. Nevertheless some small tribute must be paid to Dr. Fellowes who has been responsible for publishing so much music of the period and who has written several valuable historical studies, including one on the subject of English Cathedral Music. As Dr. Fellowes pointed out in this very book, however, there is still much to do before a definitive survey of pre-Restoration church music can be attempted. Many sources have yet to be collated and much music scored. With this in mind I began some time ago to catalogue the contents of all the known sources of early seventeenth century anthems. I would like this evening to discuss one or two points which have resulted from my work, all of which are connected, directly or indirectly, with the anthem.
The Origins and Disappearance of the English Court Ode
Authors: McGuinness Rosamond
Published: January 2007

I Ought to say, by way of introduction, that my interest in the English Court ode owes its inspiration to a paper ‘The Secular Music of John Blow’, read to this Society on 10 November 1936, by Mr. Harold Watkins Shaw, and to the questions raised by Professor Westrup in the discussion which followed.
Gustav Mahler: Prospect and Retrospect
Authors: Mitchell Donald
Published: January 2007

On 18 May, Mahler will have been dead for exactly 50 years. It is a convenient moment, perhaps, to survey, very briefly, the present state of Mahler studies and research.
The Easter Psalms of Christ's Hospital
Authors: Jeans Susi
Published: January 2007

I would like to begin my paper with a quotation from Sir John Hawkins's History of Music, because it was his short note about the music of Christ's Hospital, which set me off on my present investigation.

‘In this Hospital anno 3 Jac. a free singing school was founded and endowed by Robert Dow, … wherin, as in the College of Dulwich … the children were to be taught pricksong. These, as far as can be recollected, are the only endowments of the kind since the Reformation. At Dulwich the boys are taught musical notes, and are able to chant; but at Christ's Hospital they sing only psalm tunes, and those by ear.’
Musical Theatre in the Weimar Republic
Authors: Drew David
Published: January 2007

The Weimar republic was the outcome of the German Revolution of 1918–19, and the consequent abdication of the Kaiser. It was named after the city in which the first post-war parliament assembled. The choice of Goethe's home town was, of course, intended to have symbolic significance. On the one hand it implied a rejection of the Prussian militarist tradition centred on Berlin, while on the other it was a means of indicating a return to the values of German classical humanism. A corollary to this first session of a democratically elected parliament was the foundation in the same city of the great Bauhaus school. At least in theory, a link was established between constitutional and cultural life.
Woman in Relation to Musical Art
Authors: Stratton Stephen S.
Published: January 2007

I offer no apology for introducing this subject to the Musical Association; it possesses sufficient interest to command attention—attention that I think it has not yet received. I do not pretend that my treatment of the subject will be at all adequate to its importance, nor do I come forward to advocate the cause of woman in musical art; she is, in the present day, quite capable of taking care of herself. It is only necessary to present a fair view of her position, to clear away misconception and prejudice, and it will be seen that the subject is by no means speculative, but very tangible and real; and its discussion will, I trust, be both interesting and profitable.
Schubert's Music for the Theatre
Authors: Mckay Elizabeth Norman
Published: January 2007

To judge from the number of programmes devoted to the music of Schubert as well as numerous occasional performances of his works in other programmes on the BBC Third Network in recent months, Schubert must be one of the most popular composers at the moment. This apparent popularity is of course also evident from the extent to which his music is heard in public concerts—the ‘Great’ C Major Symphony in orchestral concerts, the quartets, the songs, the late piano sonatas and so on in recitals. Like Bach, Mozart and Beethoven, Schubert never seems to go out of fashion, but the vogue for his music certainly could not be much greater than at present. And yet, despite this popularity, and the accompanying unearthing of many of his lesser known works, one large section of his music, the music he wrote for the theatre, remains almost entirely unknown. The scores of this music for the stage are to be found in seven large volumes of the Breitkopf und Härtel Gesamtausgabe and in piles of unpublished sheets in various collections, most of them in the music libraries of Vienna.
English Solo Song, c. 1710–1760
Authors: Johnstone H. Diack
Published: January 2007

For most of us, singer and musicologist alike, English song from the death of Purcell to the Victorian ‘renaissance’ nearly two centuries later is represented by a few of the Shakespearean settings of Arne, and a small handful of such perennial favourites as Leveridge's ‘Black-ey'd Susan’, Boyce's ‘Heart of Oak’, Dibdin's ‘Tom Bowling’, and Horn's once-ubiquitous ‘Cherry ripe’. As for our knowledge of the cultural environment in which such pieces naturally have their place, that is generally more limited still. Though theatrical in origin, we may take as typical of the sort of vocal melody which was popular with early Georgian audiences, Arne's charming ‘O come, o come, my dearest’ from The Fall of Phaeton (1736). If we agree, with Ernest Walker, that such a song is, in its way, ‘a sparkling polished little gem’, then it may be fairly maintained that English song during the first half of the eighteenth century is a veritable treasure trove of delightful music—none of it very ‘great’, certainly, but much of it worthy of a better fate than the oblivion to which it has been carelessly consigned.
Domenico Dragonetti
Authors: Slatford Rodney
Published: January 2007

A short paper can give but a glimpse at the life of a professional musician who worked in London for over half a century. Baptised Domenico Carlo Maria, Dragonetti was born in the poor parish of St. Gervasio and St. Protasio (called St. Trovaso), Venice. As with most details of his early life, there are conflicting reports as to his date of birth. Vincent Novello gives 10 April 1763, but Caffi, the musical historian and friend of Dragonetti, gives 7 April. Other dates that are variously given include 1755 (a date which also appears on one of Dragonetti's bows, now in the author's possession), ‘1762 or 1764’, and 1771.
The Making of ‘Don Carlos’
Authors: Porter Andrew
Published: January 2007

In 1969 the Institute of Verdi Studies in Parma convened an international congress on the subject of Don Carlos. Fifty-two papers were read, and the proceedings fill a fat volume of over 600 pages. Two speakers had looked beyond the printed sources: Ursula Gunther had examined the autograph of Act I, in the Bibliothèque Nationale, and David Rosen had discovered, folded down in the conducting score used for the first performance, and still in the Paris Opera library, a hitherto unknown section of the Philip/Posa duet which Verdi had cut before the premiere. He also found evidence for other pre-performance cuts, in the form of stub-ends of pages which had been literally cut from both the autograph and the conducting score; some opening and closing bars remained. A few months later I found this ‘lost’ music, in the original orchestral parts, still preserved at the Opera: the cut passages had simply been stitched or pinned together, or pasted down; the same had happened in the singers' scores. Line by line, it was possible to reconstruct a good deal of totally unknown music by the mature Verdi.
An Errors-in-Variables Approach to Estimating Models with Small Area Data
Authors: Jackson John E.
Published: January 2007

Many important social science models are estimated with subnational units, such as states, congressional districts, or counties as the units of observation. These analyses may require estimates of population characteristics for these units that are not readily available from published sources. Frequently the size and number of these units make direct data collection, such as household surveys, prohibitively expensive or completely infeasible. The need is to develop methods for using more readily available data to estimate these subgroup attributes. This article presents such a method based on national-level survey data.
Stochastic Variation: A Comment on Lewis-Beck and Skalaban's “The R-Squared”
Authors: King Gary
Published: January 2007

In an interesting and provocative article, Michael Lewis-Beck and Andrew Skalaban make an important contribution by emphasizing several philosophical issues in political methodology that have received too little attention from methodologists and quantitative researchers. These issues involve the role of systematic, and especially stochastic, variation in statistical models. After briefly discussing a few points of disagreement, hoping to reduce them to points of clarification, I turn to the philosophical issues. Examples with real data follow.
Electoral Redistricting and Endogenous Partisan Control
Authors: Jackman Simon , Vella Francis
Published: January 2007

Recent efforts at estimating bias and responsiveness in electoral systems typically proceed by assigning observations to subsamples according to which party controlled the redistricting process. We show this traditional procedure to introduce selection bias into the resulting estimates of bias and responsiveness and present an alternative strategy for estimating these parameters. Using data from the state legislatures, and employing two different measures of partisan control of redistricting, we obtain results that modestly differ from those obtained with the traditional approach. Measures of control of redistricting utilizing information about the partisan intent of redistricting commissions and tribunals are exogenous to the seats-votes relationship.
Blood pressure response to isometric exercise in patients with peripheral atherosclerotic disease
Authors: Bakke Espen F. , Hisdal Jonny , Kroese Andries J. , Jørgensen Jørgen J. , Stranden Einar
Published: January 2007

Background  The purpose of this study was to compare the circulatory responses to isometric exercise in patients with peripheral atherosclerotic disease (PAD) with healthy controls.

Methods  Eleven patients with diagnosed PAD, a control group of eleven healthy young adults, and a control group of eleven healthy age‐matched adults participated. Blood pressure, heart rate, stroke volume, cardiac output, blood velocity in the brachial artery, acral skin perfusion was continuously recorded and total peripheral resistance calculated before, during and after 2 min of 40% maximum voluntary contraction of the forearm.

Results  At rest we found a consistently higher level of mean arterial pressure (MAP) and systolic pressure (SP) in the elderly, both PAD patients and elderly controls, compared with the young controls. We found no significant difference in diastolic blood pressure. Two minutes isometric handgrip exercise induced a similar increase in MAP in all three groups (patients 32·6 (17·9) mm Hg [mean (SD)], young control group 25·3 (8·9) mm Hg, age‐matched control group 36·1 (10·6) mm Hg). No significant differences were found in the other measured cardiovascular variables during isometric handgrip. Increased TPR is the main factor contributing to the increase in blood pressure in all three groups.

Conclusion  Our study indicates that the pressor response continues to be well regulated with age, also when the cardiovascular system is altered by marked atherosclerosis. The consequence is that both PAD patients and elderly controls reach higher SP values during isometric exercise due to higher SP baseline values.
Effects of Ball Groupings on Ball Passage Vibrations of a Linear Guideway Type Ball Bearing (Pitching and Yawing Ball Passage Vibrations)
Authors: Ohta Hiroyuki , Kitajima Yoshiki , Kato Soichiro , Igarashi Yutaka
Published: January 2007

The effects of ball groupings on the pitching and yawing ball passage vibrations of linear guideway type ball bearings (linear ball bearings) under low-speed operation were studied. For this study, the test linear ball bearings (which can retain the ball grouping in operation) with three types of ball groupings were manufactured, and the pitching and yawing ball passage vibrations of each test linear ball bearing were measured using a laser autocollimator. Moreover, a calculation method of the ball passage vibrations for a linear ball bearing with an arbitrary ball grouping was presented. According to the presented method the ball passage vibrations for three types of ball groupings were calculated. The experimental and calculated results show that the occurrence of the pitching and yawing ball passage vibrations was affected by the ball groupings. For the occurrence, the wave forms, and the amplitude of the pitching and yawing ball passage vibrations for the ball groupings, the calculated results based on the presented method almost matched the experimental results.
Profiling of human mesangial cell subproteomes reveals a role for calmodulin in glucose uptake
Authors: Rao Satish P. Ramachandra , Wassell Richard , Shaw M. Alexander , Sharma Kumar
Published: January 2007

Proteomics combined with cell fractionation was used to identify proteins regulated by high glucose (HG) in human mesangial cells (HMC). Total membrane and cytosolic fraction proteins derived from HMC after 7 days of HG exposure were resolved by a two-dimensional gel electrophoresis approach. DeCyder software was used to analyze the HG-induced protein spot dysregulation. In the membrane subproteome, of the 92 spots that were matched across all gels, HG induced significant downregulation of only 4 protein spots. The dysregulated spots from the membrane subproteome included binding protein (BiP), calreticulin precursor protein, a 63-kDa transmembrane protein from a ER/Golgi intermediate, and β-subunit of collagen proline 4-hydroxylase. In the cytosolic subproteome, of the 122 spots that were matched across all gels, HG induced downregulation of 3 protein spots and upregulation of 2 protein spots significantly. Enolase 1, annexin VI, and γ2-actin were decreased, whereas heat shock protein-70 kDa and calmodulin (CaM) were increased. Further confocal microscopy and Western immunoblotting of mesangial cells validated the increase in CaM. Immunoblotting of diabetic mouse and rat kidneys exhibited a marked increase in CaM at both early and late stages of diabetes, reflecting the potential physiological relevance of CaM upregulation. CaM-specific inhibitors blocked glucose transport stimulated by transforming growth factor-β and insulin in mesangial cells. In conclusion, using a combination of cell fractionation and protein expression profiling, we identified a cohort of HG-dysregulated proteins in the HMC and identified a critical and as yet unrecognized role for CaM in glucose transport in mesangial cells.
The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Induces Growth Inhibition and Enhances Gemcitabine-Induced Cell Death in Pancreatic Cancer
Authors: Arnold Nichole Boyer , Arkus Nohea , Gunn Jason , Korc Murray
Published: January 2007

Purpose: Pancreatic cancer is an aggressive human malignancy that is generally refractory to chemotherapy. Histone deacetylase inhibitors are novel agents that modulate cell growth and survival. In this study, we sought to determine whether a relatively new histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), inhibits pancreatic cancer cell growth.

Experimental Design: The effects of SAHA on the growth of three pancreatic cancer cell lines (BxPC3, COLO-357, and PANC-1) were examined with respect to cell cycle progression, p21 induction and localization, and interactions with the nucleoside analogue gemcitabine.

Results: SAHA induced a G1 cell cycle arrest in BxPC-3 cells and COLO-357 cells but not in PANC-1 cells. This arrest was dependent, in part, on induction of p21 by SAHA, as p21 was not induced in PANC-1 cells, and knockdown of p21 using small interfering RNA oligonucleotides nearly completely suppressed the effects of SAHA on cell cycle arrest in COLO-357 and partly attenuated the effects of SAHA in BxPC-3. COLO-357 and BxPC-3 cells, but not PANC-1 cells, were also sensitive to gemcitabine. In the gemcitabine-resistant PANC-1 cells, a 48-h cotreatment with SAHA rendered the cells sensitive to the inhibitory and proapoptotic effects of gemcitabine. An additive effect on growth inhibition by SAHA and gemcitabine was observed in COLO-357 and BxPC-3 cells. Moreover, analysis of p21 distribution in COLO-357 cells revealed that SAHA induced the cytoplasmic localization of both p21 and phospho-p21.

Conclusions: These data indicate that SAHA exerts proapoptotic effects in pancreatic cancer cells, in part, by up-regulating p21 and sequestering it in the cytoplasm, raising the possibility that SAHA may have therapeutic potential in the treatment of pancreatic cancer.
Explaining the Familial Colorectal Cancer Risk Associated with Mismatch Repair (MMR)-Deficient and MMR-Stable Tumors
Authors: Aaltonen Lauri , Johns Louise , Järvinen Heikki , Mecklin Jukka-Pekka , Houlston Richard
Published: January 2007

Purpose: There is a paucity of data quantifying the familial risk of colorectal cancer associated with mismatch repair (MMR)-deficient and MMR-stable tumors. To address this, we analyzed a population-based series of 1,042 colorectal cancer probands with verified family histories.

Experimental Design: Constitutional DNA from probands was systematically screened for MYH variants and those with cancers displaying microsatellite instability (MSI) for germ-line MMR mutations; diagnoses of familial adenomatous polyposis and juvenile polyposis were established based on clinical phenotype and mutational analysis. Familial colorectal cancer risks were enumerated from age-, sex-, and calendar-specific population incidence rates. Segregation analysis was conducted to derive a model of the residual familial aggregation of colorectal cancer.

Results: Germ-line predisposition to colorectal cancer was identified in 37 probands [3.4%; 95% confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic MYH variants. The risk of colorectal cancer in first-degree relatives of probands with MSI and MMR-stable cancers was increased 5.01-fold (95% CI, 3.73-6.59) and 1.31-fold (95% CI, 1.07-1.59), respectively. MSH2/MLH1 mutations were responsible for 50% of the overall excess familial risk and 80% of the risk associated with MSI cancers but 32% of the familial risk was unaccounted for by known loci. Genetic models based on major gene loci did not provide a better explanation of the residual familial aggregation than a simple polygenic model.

Conclusions: The information from our analyses should be useful in quantifying familial risks in clinical practice and in the design of studies to identify novel disease alleles.
Expression of Adipose Differentiation-Related Protein: A Predictor of Cancer-Specific Survival in Clear Cell Renal Carcinoma
Authors: Yao Masahiro , Huang Ying , Shioi Koichi , Hattori Keiko , Murakami Takayuki , Nakaigawa Noboru , Kishida Takeshi , Nagashima Yoji , Kubota Yoshinobu
Published: January 2007

Purpose: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC.

Experimental Design: A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases.

Results: ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration–positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak.

Conclusions: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.
Modifying Dendritic Cells via Protein Transfer for Antitumor Therapeutics
Authors: Liu Shanrong , Foster Barbara A. , Chen Tie , Zheng Guoxing , Chen Aoshuang
Published: January 2007

Purpose: The modification of therapeutic dendritic cells (DC) with various immunostimulatory molecules represents a useful means for improving the antitumor efficacy of DC transfer–based immunotherapy. We have evaluated the feasibility of modifying therapeutic DCs with multiple immunostimulatory molecules using a time-efficient, protein transfer (or protein “painting”)–based method.

Experimental Design: Bone marrow–derived DCs were painted with either control protein human IgG (hIgG) or three immunostimulatory molecules, SLC, 4-1BBL, and TRANCE (the triad protein). Painted DCs were injected intratumorally into mice bearing established tumors. Subsequently, the capacities of painted DCs to migrate to the draining lymph nodes, recruit the host T cells, promote Th1 cytokine responses, and elicit therapeutic antitumor responses were evaluated.

Results: The triad protein transfer yields a uniform population of DCs that coexpress all three of the proteins. Compared with the hIgG-painted DCs, the triad protein–painted DCs migrate more efficiently to the draining lymph nodes and show enhanced capabilities to induce T cell infiltration of tumors and to promote Th1 cytokine responses in vivo. Furthermore, in both the EG.7 and TRAMP-C2 tumor models, compared with the DCs painted with hIgG or only one of the three proteins, the triad protein–painted DCs, upon adoptive transfer, elicit stronger therapeutic responses against established tumors. Importantly, the antitumor responses of the triad protein–painted DCs are mediated by systemic antitumor immunity.

Conclusions: This study establishes, for the first time, the feasibility of optimizing DC transfer–based immunotherapy via combinatorial protein transfer of therapeutic DCs with an array of immunostimulatory molecules.
Age-Specific Relationship of Aortic Pulse Wave Velocity With Left Ventricular Geometry and Function in Hypertension
Authors: Schillaci Giuseppe , Mannarino Massimo R. , Pucci Giacomo , Pirro Matteo , Helou Johny , Savarese Gianluca , Vaudo Gaetano , Mannarino Elmo
Published: January 2007

Aortic pulse wave velocity (PWV), generally considered an intrinsic marker of arterial stiffness, might depend in part on the velocity of myocardial fiber shortening, but the relation between PWV and myocardial function in humans has been understudied. A total of 237 untreated hypertensive subjects over a wide age range (18 to 88 years) underwent aortic PWV determination and echocardiography, from which the mean velocity of circumferential fiber shortening was calculated as a measure of the velocity of myocardial shortening, and relative wall thickness was taken as a measure of left ventricular concentric remodeling. Patients were divided in 3 age groups (<40 years, 40 to 59 years, and ≥60 years). In the young, aortic PWV was directly associated with heart rate–corrected velocity of circumferential fiber shortening (
r
=0.39;
P
=0.002) but not to relative wall thickness (
r
=−0.01;
P
=0.95). The opposite was found in the older group, in which aortic PWV was accompanied by a concentric left ventricular geometric pattern (
r
=0.44 with relative wall thickness;
P
=0.009) and a reduced velocity of circumferential fiber shortening (
r
=−0.54;
P
<0.001) and stress-corrected midwall fractional shortening (
r
=−0.56;
P
<0.001). Intermediate values were found in the middle-aged group (
r
=0.23;
P
<0.01 with relative wall thickness;
r
=−0.07,
P
value not significant with velocity of circumferential fiber shortening). In conclusion, the relation between aortic PVW and the left ventricle is strongly age dependent. These data suggest that, in young people, aortic PWV is partly determined by an increased velocity of myocardial shortening. With increasing age, a relationship between aortic PWV (as a measure of arterial stiffness) and left ventricular concentric geometry emerges, which ultimately leads to a depressed ventricular systolic function.
A Mutation in the Fibroblast Growth Factor Receptor 1 Gene Causes Fully Penetrant Normosmic Isolated Hypogonadotropic Hypogonadism
Authors: Xu Ning , Qin Yu , Reindollar Richard H. , Tho Sandra P. T. , McDonough Paul G. , Layman Lawrence C.
Published: January 2007

Context: Kallmann syndrome (KS) consists of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia/hyposmia. Currently, the fibroblast growth factor receptor 1 (FGFR1) gene is the only known autosomal dominant cause of KS, which is also associated with synkinesia, midfacial defects, and dental agenesis.

Objective: Mutations in FGFR1 typically demonstrate reduced penetrance, variable expressivity, and until recently have been exclusively identified in families with anosmia. The purpose of this study was to determine whether FGFR1 mutations were present in a unique family with autosomal dominant, fully penetrant, normosmic IHH.

Design: The study is a review of detailed clinical findings, dynamic endocrine studies, and performance of a molecular analysis of the FGFR1 gene.

Setting: The study was carried out in an academic medical center.

Patients: All four affected individuals have complete IHH with full penetrance but no anosmia/hyposmia, and they have none of the FGFR1-associated anomalies. In addition, no other family member has anosmia.

Inverventions: Interventions included detailed phenotype characterization including history, physical exam, smell testing, dynamic pituitary testing, brain imaging, and molecular analysis.

Main Outcome Measures: Outcome was measured by the determination of the severity of IHH, olfactory function, and sequence of the FGFR1 gene.

Results: The same heterozygous nonsense mutation, Arg622X, was present in all four affected members, but not in three unaffected members or 100 controls. The mutation is predicted to encode a truncated protein or result in nonsense-mediated decay.

Conclusions: Our findings indicate that mutations in the FGFR1 gene can cause normosmic, fully penetrant, complete IHH with little or no variable expressivity, and without the other FGFR1-associated anomalies typically found in KS.
Role for WNT16B in human epidermal keratinocyte proliferation and differentiation
Authors: Teh Muy-Teck , Blaydon Diana , Ghali Lucy R. , Edmunds Scott , Pantazi Eleni , Barnes Michael R. , Leigh Irene M. , Kelsell David P. , Philpott Michael P.
Published: January 2007

WNT signalling regulates a variety of cell functions including cell fate, polarity, and differentiation via the canonical or β-catenin stabilisation pathway and/or the planar cell polarity or non-canonical pathway. We have previously demonstrated that two isoforms (A and B) from the WNT16 locus have differential expression in various adult human tissues. In this study we show that WNT16B but not WNT16A isoform was upregulated in basal cell carcinomas compared with normal skin. We further investigated the cellular and molecular functions of WNT16B in primary human epidermal keratinocytes and a keratinocyte cell line. Cellular expression of WNT16B neither stabilised β-catenin nor activated the lymphoid enhancer factor or T-cell factor transcriptional reporter in primary keratinocytes. WNT16B activated the Jun-N-terminal kinase cascade suggesting the activation of a non-canonical WNT signalling pathway. Constitutive expression of WNT16B significantly enhanced the rate of cell proliferation and prolonged clonogenicity in primary keratinocytes. Silencing WNT16B by RNA interference reduced keratinocyte proliferation. Furthermore, overexpression of WNT16B induced a hyperproliferation phenotype in an organotypical culture system. This work presents the first evidence that WNT16B activates human keratinocyte proliferation possibly via a β-catenin-independent non-canonical WNT transduction pathway.
Connexin43 increases the sensitivity of prostate cancer cells to TNFα-induced apoptosis
Authors: Wang Min , Berthoud Viviana M. , Beyer Eric C.
Published: January 2007

To examine the effects of increased expression of connexin43 (Cx43) upon cell viability and response to cytotoxic agents, we expressed Cx43 in LNCaP and PC3 prostate cancer cells by infection with a recombinant adenovirus (Ad-Cx43). Infection with Ad-Cx43 led to the formation of Cx43-containing gap junction plaques at appositional membranes and increased Lucifer Yellow transfer in LNCaP cells, but not in PC3 cells. The increased intercellular communication was blocked by co-infection with an adenovirus containing a dominant-negative Cx43 (Ad-Cx43DN). Infection of LNCaP (but not PC3) cells with Ad-Cx43 greatly increased their sensitivity to killing by tumor necrosis factor α (TNFα), anti-Fas antibodies, and TRAIL as quantified using an MTS assay. The TNFα-induced cell death was dependent on cell density, and it was associated with increased annexin V staining, an increased proportion of sub-G1 cells, and activation of caspase 8. The TNFα-induced effects on Ad-Cx43-infected LNCaP cells were blocked by co-infection with Ad-Cx43DN or by pre-incubation with neutralizing antibodies directed against TNFα receptor 1. These results demonstrate that TNFα induces apoptosis in LNCaP cells by signaling through TNFα receptor 1 and that expression of functional Cx43 gap junction channels increases their sensitivity to TNFα.
Mutation Scanning the GJB1 Gene with High-Resolution Melting Analysis: Implications for Mutation Scanning of Genes for Charcot-Marie-Tooth Disease
Authors: Kennerson Marina L , Warburton Trent , Nelis Eva , Brewer Megan , Polly Patsie , De Jonghe Peter , Timmerman Vincent , Nicholson Garth A
Published: January 2007

Background: X-linked Charcot-Marie-Tooth type 1 disease has been associated with 280 mutations in the GJB1 [gap junction protein, beta 1, 32kDa (connexin 32, Charcot-Marie-Tooth neuropathy, X-linked)] gene. High-resolution melting analysis with an automated instrument can be used to scan DNA for alterations, but its use in X-linked disorders has not been described.

Methods: A 96-well LightScanner for high resolution melting analysis was used to scan amplicons of the GJB1 gene. All mutations reported in this study had been confirmed previously by sequence analysis. DNA samples were amplified with the double-stranded DNA-binding dye LC Green Plus. Melting curves were analyzed as fluorescence difference plots. The shift and curve shapes of melting profiles were used to distinguish controls from patient samples.

Results: The method detected each of the 23 mutations used in this study. Eighteen known mutations provided validation of the high-resolution melting method and a further 5 mutations were identified in a blind study. Altered fluorescence difference curves for all the mutations were easily distinguished from the wild-type melting profile.

Conclusion: High-resolution melting analysis is a simple, sensitive, and cost-efficient alternative method to scan for gene mutations in the GJB1 gene. The technology has the potential to reduce sequencing burden and would be suitable for mutation screening of exons of large multiexon genes that have been discovered to be associated with Charcot Marie Tooth neuropathy.
Physician Advice About Being Overweight: Association With Self-Reported Weight Loss, Dietary, and Physical Activity Behaviors of US Adolescents in the National Health and Nutrition Examination Survey, 1999–2002
Authors: Kant Ashima K. , Miner Patricia
Published: January 2007

OBJECTIVE. The goal was to examine the association of physician counseling about being overweight with attempted weight loss, dietary, and physical activity/inactivity behaviors of US teens.

METHODS. We used data from the National Health and Nutrition Examination Surveys 1999–2000 and 2001–2002 for 16- to 19-year-old subjects with BMI for age of ≥85th percentile (n = 716). Regression methods were used to examine the association of physician advice about teen weight status with covariate-adjusted differences in reported weight loss, dietary, and physical activity behaviors.

RESULTS. Approximately 51% of overweight teens (BMI for age of ≥95th percentile) but only 17% of at-risk teens (BMI for age of 85th to <95th percentile) reported that they had been informed by a doctor about being overweight. More than 60% of those told by a doctor about being overweight had attempted weight loss in the past year, relative to 41% of those who did not receive this advice. Teens informed of their overweight status reported significantly smaller amounts of all foods and beverages and lower energy intake per kilogram of body weight in the 24-hour recall, relative to the comparison group. Physical activity and inactivity behaviors were unrelated to professional counseling about overweight status.

CONCLUSION. Physician counseling regarding adolescent overweight status was associated with a positive impact on attempted weight loss and moderate dietary behaviors.
The Economics of Routine Childhood Hepatitis A Immunization in the United States: The Impact of Herd Immunity
Authors: Armstrong Gregory L. , Billah Kaafee , Rein David B. , Hicks Katherine A. , Wirth Kathleen E. , Bell Beth P.
Published: January 2007

OBJECTIVES. Because of the herd-immunity phenomenon, the benefits of immunization against hepatitis A extend beyond those received by those who are vaccinated. This analysis estimates the impact of herd immunity on the cost-effectiveness of routine hepatitis A immunization among US children.

PATITENS AND METHODS. In an economic model, the costs and benefits of hepatitis A immunization were estimated for immunizing all US children at age 1 year over a 10-year period starting in 2005. The future burden of disease from hepatitis A was also estimated with this model, and the fraction that would be prevented by herd immunity was modeled by using a previously published analysis of the relationship between hepatitis A vaccination coverage and declines in hepatitis A incidence.

RESULTS. Without accounting for herd-immunity effects, the costs of routine immunization would average $32000 per quality-adjusted life-year gained for the first 10 cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects would be expected to produce substantial additional benefits, lowering the cost of the immunization program to $1000 per quality-adjusted life-year gained for the first 10 cohorts. Herd-immunity benefits would be greatest for the first few cohorts, more than doubling the benefits of immunization, and would decline over time. In a univariate sensitivity analysis, estimates were most sensitive to vaccination costs but remained below $20000 per quality-adjusted life-year under all of the assumptions.

CONCLUSIONS. Herd-immunity effects more than double the savings from hepatitis A immunization during the first 10 years of the program. After accounting for these effects, immunization is close to cost-neutral on a cost-per-quality-adjusted-life-year basis.