bluuebunny/crossref_metadata_2025 huggingface dataset:
III. Of the motion of the stomach, observ'd in in a dog, in July, 1685
Authors: Pitt Christopher
Published: December 2006

1. Anatomists in their Description of Man's Body, tho' they sometimes Make mention of the Motion of the Stomach, (as in Vomiting and in conveying the Meat that is Digested in the Stomach into the Intestines) yet giving no particular Description of it from the Testimony of Sight, I hope it will be no ways impertinent in me to give an Account of it, as it appear'd to me in the Dissection of a Dog, in
July
, 1685.
V. Remarks concerning factitious salts; drawn from a discourse written by Sen. Francisco Redi
Authors: Redi Sen. Francisco
Published: December 2006

The Happy Genius of the Cardinal
de Medici
favouring and promoting Mathematical and Philosophical Studies, as well as others, makes him among his most weighty Affairs, not pass by such things as may serve the Virtuoso's as well for Private as Publick Advantage, hence it is that Seignior
Francis Redi
has been induced to collect divers Writings and Observations made some Years past in
Florence
, about Vegetable Salts; which being not ready to be published, you will here receive an Extract of them, for the Satisfaction of the Improvement of Natural Knowledge, being hereby conducted into the Manner of extracting the Salts, their Quantity and Different Figures, as like wife their Virtue and Purging Quality.
VI. A letter from Dr. Rob. Conny, to the late Dr. Rob. Plot, F. R. S. concerning a shower of fishes
Authors: Conny Rob.
Published: December 2006

Since my last to you I have received an Account of the prodigious Rain you long ago desired of me, and this Opportunity offering of conveying it safely to you I wou'd no longer delay it, and had I received the Account as you promised me of that of the Herrings, I might possibly have said somewhat more, but I shall now leave that to you.
III. Part of a letter from Mr. Witsen, Burgermaster of Amsterdam, and F. R. S. To Dr. Martin Lister, fellow of the Colledge of Physicians and R. S. Concerning some late observations in Nova Hollandia
Authors: Witsen Nicolaus
Published: December 2006

Here is returned a Ship, which by our
East-India
Company, was sent to the South Land, called,
Hollandia Nova
.
VI. Excerpta ex literis D. Cassini ad P. Fontenay mathematicum regium apud sinos
Authors: Cassini D
Published: December 2006

QuÆ circa tuam observationem Mercurii in Sole Cantone habitam meditatus eram, videre potuisti in Academiæ Regiæ Commentariis, 15 Maii, 1693.
VIII. An account of a gall-bee, and the deathwatch.
Authors: Allen Benjamin
Published: December 2006

In those Galls which came to me by the Name of Aleppo-Galls, which the insects had not eat their Way out of, I found one sort of Bee, resembling the small sort of our wild Bees which Earth; they have long; Wings, a deep Belly, and on the Back near the Comissure to the Body, it is of a greenish black, the rest redish, near a Cinnamon Colour, the Belly thick and deep.
XI. Some experiments about freezing
Authors: Desmasters
Published: December 2006

A Tube of ¼ of an Inch Diameter being fill'd with Water to the height of two Inches, and set to freeze in a Mixture of Snow and Salt, the Water, when perfectly frozen, appear'd 5/16 of an Inch, above the Mark it stood at before freezing.
II. Remarks by Mr. James Petiver, Apothecary, and Fellow of the Royal Society, on some animals, plants &c. Sent to him from Maryland, by the Reverend Mr. Hugh Jones
Authors: Petiver James , Jones Hugh
Published: December 2006

T
estudo terrestris
Americana,
dorso elato
. I do not find this certainly
described
by any Author.
III. Further experiments about freezing
Authors: Desmasters
Published: December 2006

In the Account given
Numb
. 245.
p
. 384. concerning the Expansion of Water by Freezing, the Water then made use of in these Tryals, was, a sort of rough Pump-Water;
V. Part of a letter from Dr. Musgrave, Fellow of the College of Physicians and R. S. to Dr. Sloane; concerning a piece of antiquity lately found in Somersetshire
Authors: Musgrave William
Published: December 2006

I Enclose, to you, the Figure (
see Fig
. 4.) of a curious piece of Antiquity, lately found near
Ashelney
in
Somersetshire
; the Place where King
Alfred
built, as
Milton
affirms, a
Fortress
: But according to
William
of
Malmsbury
, a
Monastery
;
VII. Part of a letter of Mr. Dale from Braintree, Feb. 1. 1699, to Dr.Martin Lister, Fellow of the College of Physicians and R. S.concerning several insects
Authors: Dale  , Lister Martin
Published: December 2006

Last summer being on our sea-coast at Harwich, I observed no less than five or six species of cochlea marine two of which I have since found to be already noted by you in your excellent hist.
II. Some observations made at a meeting of the Royal Society, concerning some wonderful contrivances of nature in a family of plants in Jamaica, to perfect the individuum, and propagate the species, with several instances analogous to them in European vegetables.
Authors: Sloane Hans
Published: December 2006

The many contrivances of nature, or rather the Supreme Being, who created, and orderly disposed all things, to bring to perfection several vegetables and animals
VIII. Part of a letter from Mons. Geoffroy, F. R. S. Dated Paris, March 7.1699, N. S. to Dr. Sloane, giving an account of the new regulations of the Royal Academy of Sciences, at Paris
Authors: Geoffroy Claude Joseph
Published: December 2006

I Shall here give you an Account of the great Splendour that the
Academie des Sciences
has Received by the Regulations, Incouragement, and Orders, Mons.
L'abbe Bignon
has obtained to it from the King.
III. A discourse of the operation of a blister when it cures a fever, made at a meeting of the Royal Society,
Authors: Cockburn William
Published: December 2006

In Pursuance of an Order of this Society, I shall Endeavor to Entertain you with a reasonable Account,
How the Raising of a Blister may Cure a Fever, and its most terrible Symptom the Delirium, and that in Six, Eight, or Ten Hours
.
III. An account of the Moorish way of dressing their meat (with other remarks) in West Barbary, from Cape Spartel to Cape de Geer
Authors: Jones Jezreel
Published: December 2006

The
Mauritanian
or
Barbarian Moor
, when he rises in the Morning, washes himself all over, and dresses, then goes to their
Jiama
, or Church, says his Prayers, and returns home
IV. Some observations of the mercury's altitude, with the changes of the weather at Emüy in China. Lat. 24° 20'. No
Authors: Cunningham James
Published: December 2006

From the I
st
. to the 8
th
. fair and clear Weather, the Mercury's Altitude, 29 14/20 Digit.
V. Part of a letter from Dr. David Gregory, to Dr. Sloane, dated Oxford, October 12. 1699. containing his observations of the eclipse of the sun on the 13th of September last
Authors: Gregory David
Published: December 2006

I send you a scheme of the phases of the late Eclipse of the Sun, (
see the Table
) as I observ'd them.
I. Part o two letters from Dr James Brewer to Dr Sloane, concerning beds of Oyster-shells found near Reading in Barkshire
Authors: Brewer James
Published: December 2006

I ask your pardon that I am so late in performing my promise in sending you the Oyster-shells.
V. Part of a journal kept from Scotland to New Caledonia in Darien, with a short account of that country
Authors: Wallace David James
Published: December 2006

September 2. We weighed at
Madera
, and were under the Tropic of
Cancer
by the 10th of the month, at which time the usual ceremony of Ducking from the Yards arm was performed on those that could not pay their Tropick Bottle.
I. A letter from Mr Bussiere, F. R. S. concerning a substance cough'd up resembling the vessels of the lungs
Authors: Buissiere Paul
Published: December 2006

Sir, Here is an observation which will prove how useful the opening of dead bodies is to Physicians and Surgeons.
II. A letter of Dr Wallis to Min Heer Leibnitz at Hannover, concerning some easy methods of his, for the measuring of curve-lined figures, plain and solid
Authors: Wallis John
Published: December 2006

Literas Tuas (Vir Celeberrime) Nov. 28. ad me datas, accepi non ita pridem: Quibus quod non prius responderim, Te veniam oro.
III. An account of part of a collection of curious plants and drugs, lately given to the Royal Society by the East India Company
Authors: Petiver James
Published: December 2006

At the beginning of the 20th Volume of these Papers, an Account was Promised of a
Curious Collection
of
Plants
and other
Simples
, gathered by Mr.
Samuel Brown
, a Physician at
Fort St George
in the
East Indies
.
VIII. A letter from Dr. P. Silverstre, of the Coll. of Phy, & F. R. S. to the publisher, giving an account of some new books and manuscripts in Italy
Authors: Silvestre Pierre
Published: December 2006

In general, every thing is very much cool'd here since the death of
Malpighi
, there are scarce any who apply themselves to the study of Nature.
I. An account of an extraordinary aneurisma of the arteria aorta near to the easis of the heart, with the symptoms thereof; dissected by Mr Lasage, surgeon, on the 10th of April, 1700
Authors: Lasage
Published: December 2006

Fifteen years ago, one John Potin, French-man, then servant to my Lord Culpeper, got a fall, which caused him a heavy pain in the breast for a while.
IV. Reverendi D. Johannis Craig, epistola ad editorem continens solutionem duorum problematum
Authors: Craig D. Johannis
Published: December 2006

M
itto tibi, vir clarissime, solutiones, duorum Problematum; quibus solvendis operam dederunt (& etiamnum dant) Celeberrimi bujus ætatis Mathematici.
VI. A letter from Dr Martin Lister, F. R. S. to Dr Tancred Robinson, F. R. S. concerning pouder'd blues passing the lacteal veins, &c
Authors: Lister Martin
Published: December 2006

When I was the other day in Town, I was shewn by you a most ingenious little Tract of Fevers: which I read over with delight.
III. An account of Mr Sam. Brown, his third book of East India plants, with their names, vertues, description, &c. By James Petiver, Apothecary, and Fellow of the Royal Society. To which are added some animals sent him from those parts
Authors: Brown Sam. , Petiver James
Published: December 2006

These were gathered between the 22th and 27th of March, 1696. at
Chamberamback
and
Aumerampead
, 14 or 16 miles from Fort St George: Dry ground generally, and good soil.
II. A letter from Mr Anthony van Leeuwenhoek, F. R. S. Concerning spiders, their way of killing their prey, spinning their webbs, generation, &c
Authors: Leeuwenhoek Antoni Van
Published: December 2006

A certain Gentleman sitting in his Garden, and observing a Spider of a blackish colour, and its Body like Chagrine Leather, took a small Twig, and Pressing it therewith, out of the upper part of the Body there came forth a great number of small Spiders.
IV. A description of a new kind of walnut tree, discovered by Monsieur Reneaume, of the Royal Academy of Sciences
Authors: Reneaume
Published: December 2006

The Walnut-tree, which the
Greeks
called sometimes Xάςvæ Bασιλιxῂ, and sometimes Πεςσιxῂ, in
Latin Nux Juglans sive regia
, is a Tree known to every Body.
III. An account of the strange effects of the varnish. Wrote by Dr Joseph Del Papa, physician to the Cardinal De Medices, at the desire of the great duke of Tuscany. Communicated by Dr William Sherard
Authors: Papa del Joseph Dr
Published: December 2006

The using and handling of the
Indian
Varnish (or Lackar) so far as is necessary to apply or lay it on subjects to be varnisht, having produced such extraordinary effects on signior
Ignatio
, and more remarkably on his maid Servant,
viz
.
III. Part of a letter from the Reverend Mr Abraham de la Pryme to the publisher, concerning trees found under ground in Hatfield Chace
Authors: Pryme Abraham De La
Published: December 2006

Honoured Sir, It hath been the good Providence of God to settle me in this part of the Country, where near abouts I was bred and born (and therefore may write with more assuredness thereof, than any one can from a superficial and transitory view and enquiry) to wit, at the Ancient Town of
Thorn
, within the famous Levels of
Hatfield
Chace (so well known in the Courts of
westminster
, for the great Suits that have been depending there about them, this threescore and ten years) which Levels were the greatest Chace of Red Dear that K.
Ch
.
VII. An account of a woman, who voided the greatest part of a fœtus by the nnvel
Authors: Birbeck Christopher
Published: December 2006

One
Raper
's Wife, in a Town called
Coxwold
, 12 miles from
York
, falling in Labour of Child Birth, the Midwife using her endeavour extracted the Secundine, it offering first, and could not by her best skill perceive any thing else remaining:
I. An account of the taking and taming of elephants in zeylan, by Mr Strachan, a physician, who lived 17 years there
Authors: Strachan
Published: December 2006

All the Natives within 20 miles from the Sea-coast betwixt
Matura
and
Negumbo
are subject to the
Hollanders
, and know the Duty and Service which their East-India Company requires of them.
VI. Part of some letters from Mr Christopher Hunter to Dr Martin Lister, F. R. S. concerning several Roman inscriptions, and other antiquitios in Yorkshire.
Authors: Hunter Christopher Alexander
Published: December 2006

Sir, I Humbly beg pardon for so long delaying to absolve the promise I formerly made of presenting you with an account of another Roman Station in the County of Durham, at a Village call'd Ebchester: but tho I was born near that place, and since my promise have often carefully view’d it, I cou’d not till very lately satisfie my self so far as to beable to reduce my mind from the vulgar opinion, that this has never been more than a Place nam’d from that Pious Virgin St Ebba, which is all Mr Cambden says of it.
II. Part of some letters from Mr Anthony van Lewuenhoeck, F. R. S. to the Royal Society, and the Right Honourable the Lord Somers their president, containing several microscopical observations and experiments concerning the animalcula in semine masculino of cocks and spiders, shortness of breath, &c.
Authors: Leeuwenhoek Antoni Van
Published: December 2006

I Take the Liberty of sending your Lordship some little Figures and Observations which I made partly the last year, and partly this.
II. A discourse concerning some influence of respiration on the motion of the heart, hitherto unobserved
Authors: Drake James
Published: December 2006

Tho divers accurate Treatises of the
Heart
and action, have been written by Learned Men of several Nations, especially by two of our own Country; the Great
Dr. Harvey
, to whose happy Sagacity this Nation owes the Glory of the Invention of the
Circulation
of the
Blood
;
III. A Letter from Dr Thomas Molyneux, F. R. S. to the Right Reverend St George, Lord Bishop of Clogher in Ireland, containing some thoughts concerning the ancient Greek and Roman lyre, and an explanation of an obscure passage in one of Horace's odes.
Authors: Molyneux Thomas
Published: December 2006

My very much Honour'd Lord. Out of the abundance of your good nature, and the undeserved kindness you have always shewed me, your Lordship has formerly been pleased, not to dislike some Thoughts I have communicated to you on several Subjects, as they occasionally came in my way;
II. An abstract of part of a letter from Dr Bonomo to Signior Redi, containing some observations concerning the worms of humane bodies.
Authors: Bonomo Dr , Mead Richard
Published: December 2006

Having frequently observed that the Poor Women when their Children are troubled with the Itch, do with the point of a Pin pull out of the Scabby Skin little Bladders of Water, and crack them like Fleas upon their Nails; and that the Scabby Slaves in the Bagno at Leghorne do often practice this Mutual Kindness upon one another; it came into my Mind to examine what these Bladders might really be.
I. A letter to Dr John Wright, F. Col. Phys. Lond. to Mr Wm Cowper, F. R. S. concerning the cure of an apostemation of the lungs
Authors: Cowper William , Wright John
Published: December 2006

Sir, According to your desire, I send you the Case of Mrs
Jane Terry
, Niece to Mt
Fowkes
in
Cursitors-Ally
, near
Lincolns-Inn
and thank you for your assistance in her Cure, to which your extraordinary skill in your Profession very much contributed.
III. Some new observations upon the parts and use of the flower in plants.
Authors: Morland Samuel
Published: December 2006

The nice and ourious Texture of the Flower and its Furniture, obvious to common view, hath invited and employ'd the enquiries of many Learned and Sagacious Persons.
V. Experimentum anatomicum ad veram dure & matris motus cansam detegendam institutum, ab H. Ridley. M. D. & Reg. Coll. Medic. Lond. Socio. Sept. 20. 1703
Authors: Ridley H
Published: December 2006

Cum Novan Plane, & ab ea quam olim in
Anatomiamea de Cerebro Cap
. 6. evulgate Protulearam alienam, de motu illo Duræ matris reciproeo qui in vulneribus cerebri, vel in Animalium vivorum sectione visui fe offert, a Cl. Viro Domino Georgio Baglivo Theor.
in Roman Archilyc
.
Novel Transcription Factors Are Induced by Chronic Cocaine Treatment
Authors: HOPE BRUCE T.
Published: December 2006

There are many other transcription factors that are regulated by cocaine, and there are several nontranscriptional mechanisms of regulating protein levels as well. However, the induction of the chronic AP‐1 complex and the chronic Fras provides a mechanism capable of underlying long‐lasting alterations in gene expression following chronic cocaine treatment. We hypothesize that while the well‐known acute effects of cocaine are occurring, the acutely induced cAMP pathway, possibly in conjunction with other second messenger pathways, is also inducing two general types of alterations in gene expression. 1. Acutely induced significant alterations in gene expression are rapidly induced and relatively short‐lived. These alterations in gene expression would allow the cell to rapidly adapt to cocaine in its environment without committing to long‐term changes. 2. Additional alterations in gene expression are induced by each acute administration during chronic cocaine exposure. These latter alterations are gradually induced and long‐lasting. With each acute activation, the level of induction of these latter longer‐lasting alterations in gene expression would be relatively small and insignificant compared to the rapidly induced acute alterations in gene expression. Therefore, with each acute administration, the cell does not commit itself to long‐term alterations. However, these small but longer lasting changes in gene expression would accumulate with each acute administration during chronic cocaine treatment, similar to the accumulation of the chronic AP‐1 complex (Fig. 4). The cumulative alterations which occur during repeated administrations eventually reach a level where they produce significant and long‐lasting alterations in gene expression different from those induced acutely. This incremental induction of long‐lasting alterations in gene expression would allow the cell to gradually commit to long‐term alterations for the purpose of adapting to repeated long‐term exposure to cocaine in its environment. These long‐lasting alterations in gene expression may underlie the gradual induction of persistent changes in protein levels, neuronal signaling, and related behaviors. This hypothesis allows for the different adaptations observed following acute versus chronic cocaine administration at the biochemical, physiological, and behavioral levels.

We hope these investigations provide ideas for specific pharmacological blockade or reversal of the long‐term, versus short‐term, alterations in gene expression that lead to addiction, without interfering with the animal's or human's ability to experience reward. This would be important for ensuring both efficacy and compliance.
Metrisation, Topological Groups, and Compacta
Authors: COLLINS P.J. , GARTSIDE P.M.
Published: December 2006

The paper discusses metrisation and generalised metric space properties of topological groups and compacta, with special reference to recent work of Cairns on reflection theorems, of Cairns, Knight, and Rudin on monotone normality, and of Gartside and Rezničenko on set‐Mal'tsev operators and stratifiable topological groups.
On the Completion of a MAP Group
Authors: GALINDO JORGE , HERNÁNDEZ SALVADOR
Published: December 2006

The following question is adressed in this paper: Given a maximally almost periodic (MAP) group, is the bilateral Raǐov completion of G also a MAP group?

It is proved by means of an example that the answer is negative in general. Then a characterization of the MAP groups having a MAP completion is obtained so that some sufficient conditions follow from it.
A Minimal Sober Topology Is Always Scott
Authors: MCCLUSKEY A.E. , McCARTAN S.D.
Published: December 2006

Given the lattice of all topologies definable for an infinite set X, we employ he well‐developed contraction technique (of intersecting a given topology with a suitably chosen principal ultratopology) for solving many minimality problems. We confirm its potential in characterising and, where possible, identifying those topologies which are minimal with respect to certain separation axioms, notably that of sobriety and its conjunction with various other axioms. Finally, we offer an alternative description of each topologically established minimal structure in terms of the behavior of the naturally occurring specialization order and the intrin sic topology on the resulting partially‐ordered set.
Shoemaker‐Levy 9 and Plume‐forming Collisions on Eartha
Authors: BOSLOUGH MARK B. E. , CRAWFORD DAVID A.
Published: December 2006

ABSTRACT: Computational models for the July, 1994 collision of comet Shoemaker‐Levy 9 with Jupiter have provided a framework for interpreting the observational data. Imaging, photometry, and spectroscopy data from ground‐based, Hubble Space Telescope, and Galileo spacecraft instruments are consistent with phenomena that were dominated by the generation of incandescent fireballs that were ballistically ejected to high altitudes, where they formed plumes that subsequently collapsed over large areas of Jupiter's atmosphere. Applications of similar computational models to collisions into Earth's atmosphere show that a very similar sequence of events should take place for NEO impacts with energies as low as 3 megatons, recurring on 100 year timescales or less. This result suggests that the 1908 Tunguska event was a plume‐forming atmospheric explosion, and that some of the phenomena associated with it might be related to the ejection and collapse of a high plume. Hazards associated with plume growth and collapse should be included in the evaluation of the impact threat to Earth, and opportunities should be sought for observational validation of atmospheric impact models by exploiting data already being collected from the natural flux of multikiloton to megaton sized objects that constantly enter Earth's atmosphere on annual to decadal timescales.
Target Earth: Evidence for Large‐scale Impact Eventsa
Authors: GRIEVE RICHARD A. F.
Published: December 2006

ABSTRACT:Unlike the Moon, the Earth has retained only a small sample of its population of impact structures. Currently, over 150 impact structures are known and there are 15 instances of impact known from the stratigraphic record, some of which have been correlated with known impact structures. The terrestrial record is biased toward younger and larger structures on the stable cratonic areas of the crust, because of the effects of constant surface renewal on the Earth. The high level of endogenic geologic activity also affects the morphology and morphometry of terrestrial impact structures; although, the same general morphologic forms that occur on the other terrestrial planets can be observed. A terrestrial cratering rate of 5.6 ± 2.8 × 10−15km−1a−1for structures ≥ 20 km in diameter can be derived, which is equivalent to that estimated from astronomical observations. Although there are claims to the contrary, the overall uncertainties in the ages of structures in the impact record preclude the determination of any periodicity in the record. Small terrestrial impact structures are the result of the impact of iron or stony iron bodies, with weaker stony and icy bodies being crushed on atmospheric passage. At larger structures (> 1 km), trace element geochemistry suggests that ∼50% of the impact flux is from chondritic bodies, but this may be a function of the signal:noise ratio of the meteoritic tracer elements. Evidence for impact in the stratigraphic record is both chemical and physical. Although currently small in number, there are indications that more evidence will be forthcoming with time. Such searches for evidence of impact have been stimulated by the chemical and physical evidence of the involvement of impact at the K/T boundary. There will, however, be problems in differentiating geochemically the signal of even relatively large impact events from the background cosmic flux of every day meteoritic debris. Even with these biases and difficulties, the terrestrial impact record is the dominant source of ground truth information on the details of the impact flux and its known and potential effects on the evolution of the Earth and its biosphere. For although the record is poorly known, what evidence there is represents an integration over considerable geologic time. On the timescales of 105–106a, it is clear that impact represents a major threat to human civilization. Given the stochastic nature of impact, the timing of such an event is unknown.
Cognitive Impairment and Cellular/Vascular Changes in the Cerebral White Mattera
Authors: PANTONI LEONARDO , GARCIA JULIO H.
Published: December 2006

ABSTRACT: A possible relation between cerebral white‐matter injury and dementia was intuitively attributed by Alzheimer to changes affecting the small penetrating vessels that supply the cerebral white matter. Several observations support the view that white‐matter changes detectable by neuroimaging may contribute to cognitive deficits in the elderly. But many questions concerning this matter remain partially answered. In this communication we review: (1) Selected anatomic features of the blood vessels supplying the white matter; (2) possible pathogenetic mechanisms responsible for the white‐matter changes; (3) observations on humans and animals suggesting a causal relationship between ischemia/hypoxemia and white‐matter injury; (4) epidemiologic studies linking white‐matter abnormalities with cognitive disorders. We conclude that abnormalities in the small vessels caused by aging and arterial hypertension, or other processes (cerebral amyloid angiopathy, CADASIL) together with systemic circulatory disturbances, such as abrupt variations in blood pressure values or cardiac diseases, may be the substrate of selective white‐matter injury. The damage is structurally characterized by incomplete infarction or selective cellular injury.
Serum Protein Leakage in Alzheimer's Disease Revisited
Authors: MUNOZ DAVID G. , ERKINJUNTTI TIMO , GAYTAN‐GARCIA SYLVIA , HACHINSKI VLADIMIR
Published: December 2006

ABSTRACT: Leakage of serum proteins into the brain parenchyma has been repeatedly used as evidence of blood‐brain barrier (BBB) damage in experimental and human studies. However, there is no consensus in the literature concerning this phenomenon in Alzheimer's disease (AD). We have examined this question by comparing frontal lobe sections in seven groups of patients: Multi‐infarct dementia (n= 6), AD with (n= 10) and without (n= 10) infarcts, age‐matched controls with (n= 10) and without (n= 10) infarcts, controls with neurodegenerative diseases other than AD, and young controls (n= 10). An additional series compared prospectively followed patients with a diagnosis of either multi‐infarct dementia (n= 5) or AD (n= 4). Albumin was detected in white‐matter astrocytes in all cases, without significant variation in intensity. In addition, diverse combinations of neurons, astrocytes, and (in AD patients) senile plaques were present in the cerebral cortex in an inconsistent manner. Semiquantitative analysis showed no statistically significant differences among groups. Anti‐IgG labeled astrocytes in infarcts only. Complement C3c component was detected in rare amyloid plaques in a minority (15%) of AD cases. Selective labeling of AD‐specific lesions in a patchy manner was observed for serum amyloid P. We conclude that there is no immunohistochemical evidence of alteration of the BBB in Alzheimer's disease with or without vascular factors or in old age. Serum amyloid P binds avidly to AD lesions, but our findings are consistent with leakage through the BBB during the agonal or immediate postmortem period. Finally, no specific pattern of abnormality in the BBB was detected in multi‐infarct dementia.
Interactions of β‐Amyloids with the Blood–Brain Barrier
Authors: BANKS WILLIAM A. , KASTIN ABBA J. , MANESS LAWRENCE M. , BANKS MARIAN F. , SHAYO MARCOS , McLAY ROBERT N.
Published: December 2006

ABSTRACT: Blood‐borne β‐amyloids (Aβs) could affect brain function by (1) crossing the BBB to directly interact with brain tissues or (2) altering BBB function by interacting with the brain capillaries that make up the BBB. Several radioactively labeled Aβe have been examined for such interactions. Blood‐borne Aβ1‐28 is hindered from accumulating in brain by a slow rate of passage across the BBB and by robust enzymatic degradation. Aβ1‐40, but not Aβ40‐1 or Aβ1‐42, is sequestered by brain capillaries, raising the possibility that it could affect BBB function. Small amounts of circulating Aβ1‐40 are recovered intact from CSF and brain. Aβ1‐40 is degraded by aluminum‐sensitive, calcium‐dependent intracellular enzymes. Apo‐J, which can bind Aβ, has been shown with an in situ method to be transported by a saturable system across the BBB. However, our recent work has shown that this system is not operable in vivo, probably because the transporter is saturated at physiological blood levels. In conclusion, Aβs have been shown to interact with and to cross the BBB.
Predictive Genetic Tests: Problems and Pitfalls
Authors: DAVIS JESSICA G.
Published: December 2006

ABSTRACT: The role that genetic factors play in medicine has expanded, owing to such recent advances as those made by the Human Genome Project and the work that has spun off from it. The project is focusing particularly on localization and characterization of recognized human genetic disorders, which in turn increases awareness of the potential for improved treatment of these disorders. Technical advances in genetic testing in the absence of effective treatment has presented the health profession with major ethical challenges. The example of the identification of the BRCA1 and BRCA2 genes in families at high risk for breast and ovarian cancer is presented to illustrate the issues of the sensitivity of the method, the degree of susceptibility a positive result implies, the need for and availability of counseling and patient education, and confidentiality of the test results. A compelling need exists for adequate education about medical genetics to raise the “literacy” rate among health professionals.
Effect of Lithium Maintenance on. Suicidal Behavior in Major Mood Disordersa
Authors: TONDO LEONARDO , JAMISON KAY R. , BALDESSARINI ROSS J.
Published: December 2006

Abstract We reviewed evidence of a possible antisuicide action of lithium maintenance treatment in mood disorders. Of 28 published studies involving over 17,000 patients with major affective illnesses, most yielded supportive evidence: risk of suicides and attempts averaged 3.2 versus 0.37 per 100 patient‐years without versus with lithium (8.6‐fold difference). In a new study of 284 bipolar I‐ and II‐disordered patients, corresponding rates (2.2 vs. 0.39/100 patient‐years) differed by 5.6‐fold (p< 0.001); moreover, after disocontinuing lithium rates of suicidal acts rose by 7‐fold (16‐fold within the first year), and fatalities increased by nearly 9‐fold. Lithium maintenance treatment in recurring major mood disorders has strong evidence of antisuicide effects not demonstrated with any other mood stabilizer. Close association of suicide and depression in bipolar disorder emphasizes the need for improved identification and treatment of bipolar depression.
Asbestos Redirects Nitric Oxide Signaling through Rapid Catalytic Conversion to Nitrite
Authors: Thomas Douglas D. , Espey Michael G. , Pociask Derek A. , Ridnour Lisa A. , Donzelli Sonia , Wink David A.
Published: December 2006

Asbestos exposure is strongly associated with the development of malignant mesothelioma, yet the mechanistic basis of this observation has not been resolved. Carcinogenic transformation or tumor progression mediated by asbestos may be related to the generation of free radical species and perturbation of cell signaling and transcription factors. We report here that exposure of human mesothelioma or lung carcinoma cells to nitric oxide (NO) in the presence of crocidolite asbestos resulted in a marked decrease in intracellular nitrosation and diminished NO-induced posttranslational modifications of tumor-associated proteins (hypoxia-inducible factor-1α and p53). Crocidolite rapidly scavenged NO with concomitant conversion to nitrite (NO2−). Crocidolite also catalyzed the nitration of cellular proteins in the presence of NO2− and hydrogen peroxide. Nitrated protein adducts are a prominent feature of asbestos-induced lung injury. These data highlight the ability of asbestos to induce phenotypic cellular changes through two processes: (a) by directly reducing bioactive NO levels and preventing its subsequent interaction with target molecules and (b) by increasing oxidative damage and protein modifications through NO2 production and 3-nitrotyrosine formation. (Cancer Res 2006; 66(24): 11600-4)
G-Quadruplexes Induce Apoptosis in Tumor Cells
Authors: Qi Haiyan , Lin Chao-Po , Fu Xuan , Wood Laurence M. , Liu Angela A. , Tsai Yuan-Chin , Chen Yongjie , Barbieri Christopher M. , Pilch Daniel S. , Liu Leroy F.
Published: December 2006

Several G-rich oligodeoxynucleotides (ODNs), which are capable of forming G-quadruplexes, have been shown to exhibit antiproliferative activity against tumor cell lines and antitumor activity in nude mice carrying prostate and breast tumor xenografts. However, the molecular basis for their antitumor activity remains unclear. In the current study, we showed that a variety of telomeric G-tail oligodeoxynucleotides (TG-ODNs) exhibited antiproliferative activity against many tumor cells in culture. Systematic mutational analysis of the TG-ODNs suggests that the antiproliferative activity depends on the G-quadruplex conformation of these TG-ODNs. TG-ODNs were also shown to induce poly(ADP-ribose) polymerase-1 cleavage, phosphatidylserine flipping, and caspase activation, indicative of induction of apoptosis. TG-ODN–induced apoptosis was largely ataxia telangiectasia mutated (ATM) dependent. Furthermore, TG-ODN–induced apoptosis was inhibited by the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. Indeed, TG-ODNs were shown to activate the JNK pathway in an ATM-dependent manner as evidenced by elevated phosphorylation of JNK and c-Jun. Interestingly, a number of G-quadruplex ODNs (GQ-ODN) derived from nontelomeric sequences also induced ATM/JNK-dependent apoptosis, suggesting a possible common mechanism of tumor cell killing by GQ-ODNs. (Cancer Res 2006; 66(24): 11808-16)
Antitumor Effect of 2-Methoxyestradiol in a Rat Orthotopic Brain Tumor Model
Authors: Kang Seung-Hee , Cho Heidi T. , Devi Sarojini , Zhang Zhaobin , Escuin Daniel , Liang Zhongxing , Mao Hui , Brat Daniel J. , Olson Jeffrey J. , Simons Jonathan W. , LaVallee Theresa M. , Giannakakou Paraskevi , Van Meir Erwin G. , Shim Hyunsuk
Published: December 2006

Grade 4 malignant glioma (GBM) is a fatal disease despite aggressive surgical and adjuvant therapies. The hallmark of GBM tumors is the presence of pseudopalisading necrosis and microvascular proliferation. These tumor cells are hypoxic and express hypoxia-inducible factor-1 (HIF-1), a prosurvival transcription factor that promotes formation of neovasculature through activation of target genes, such as vascular endothelial growth factor. Here, we evaluated whether 2-methoxyestradiol, a microtubule and HIF-1 inhibitor, would have therapeutic potential for this disease in a 9L rat orthotopic gliosarcoma model using a combination of noninvasive imaging methods: magnetic resonance imaging to measure the tumor volume and bioluminescence imaging for HIF-1 activity. After imaging, histologic data were subsequently evaluated to elucidate the drug action mechanism in vivo. Treatment with 2-methoxyestradiol (60–600 mg/kg/d) resulted in a dose-dependent inhibition of tumor growth. This effect was also associated with improved tumor oxygenation as assessed by pimonidazole staining, decreased HIF-1α protein levels, and microtubule destabilization as assessed by deacetylation. Our results indicate that 2-methoxyestradiol may be a promising chemotherapeutic agent for the treatment of malignant gliomas, with significant growth inhibition. Further studies are needed to assess the effect of low or intermediate doses of 2-methoxyestradiol in combination with chemotherapeutic agents in clinical studies focused on malignant gliomas. In addition to showing tumor growth inhibition, we identified three potential surrogate biomarkers to determine the efficacy of 2-methoxyestradiol therapy: decreased HIF-1α levels, α-tubulin acetylation, and degree of hypoxia as determined by pimonidazole staining. (Cancer Res 2006; 66(24): 11991-7)
Diverse Gene Expression and DNA Methylation Profiles Correlate with Differential Adaptation of Breast Cancer Cells to the Antiestrogens Tamoxifen and Fulvestrant
Authors: Fan Meiyun , Yan Pearlly S. , Hartman-Frey Cori , Chen Lei , Paik Henry , Oyer Samuel L. , Salisbury Jonathan D. , Cheng Alfred S.L. , Li Lang , Abbosh Phillip H. , Huang Tim H-M. , Nephew Kenneth P.
Published: December 2006

The development of targeted therapies for antiestrogen-resistant breast cancer requires a detailed understanding of its molecular characteristics. To further elucidate the molecular events underlying acquired resistance to the antiestrogens tamoxifen and fulvestrant, we established drug-resistant sublines from a single colony of hormone-dependent breast cancer MCF7 cells. These model systems allowed us to examine the cellular and molecular changes induced by antiestrogens in the context of a uniform clonal background. Global changes in both basal and estrogen-induced gene expression profiles were determined in hormone-sensitive and hormonal-resistant sublines using Affymetrix Human Genome U133 Plus 2.0 Arrays. Changes in DNA methylation were assessed by differential methylation hybridization, a high-throughput promoter CpG island microarray analysis. By comparative studies, we found distinct gene expression and promoter DNA methylation profiles associated with acquired resistance to fulvestrant versus tamoxifen. Fulvestrant resistance was characterized by pronounced up-regulation of multiple growth-stimulatory pathways, resulting in estrogen receptor α (ERα)–independent, autocrine-regulated proliferation. Conversely, acquired resistance to tamoxifen correlated with maintenance of the ERα-positive phenotype, although receptor-mediated gene regulation was altered. Activation of growth-promoting genes, due to promoter hypomethylation, was more frequently observed in antiestrogen-resistant cells compared with gene inactivation by promoter hypermethylation, revealing an unexpected insight into the molecular changes associated with endocrine resistance. In summary, this study provides an in-depth understanding of the molecular changes specific to acquired resistance to clinically important antiestrogens. Such knowledge of resistance-associated mechanisms could allow for identification of therapy targets and strategies for resensitization to these well-established antihormonal agents. (Cancer Res 2006; 66(24): 11954–66)
RhoA Mediates Cyclooxygenase-2 Signaling to Disrupt the Formation of Adherens Junctions and Increase Cell Motility
Authors: Chang Yu-Wen E. , Marlin Jerry W. , Chance Terry W. , Jakobi Rolf
Published: December 2006

Cyclooxygenase-2 (COX-2) represents an important target for treatment and prevention of colorectal cancer. Although COX-2 signaling is implicated in promoting tumor cell growth and invasion, the molecular mechanisms that mediate these processes are largely unknown. In this study, we show that the RhoA pathway mediates COX-2 signaling to disrupt the formation of adherens junctions and increase cell motility. Disruption of adherens junctions promotes tumor cell invasion and metastasis and is often associated with tumor progression. We detected high levels of RhoA activity in HCA-7 colon carcinoma cells that constitutively express COX-2. Inhibition of COX-2 significantly reduced the levels of RhoA activity in HCA-7 cells, suggesting that constitutive expression of COX-2 stimulates RhoA activity. Interestingly, inhibition of COX-2 or silencing of COX-2 expression with small interfering RNA (siRNA) stimulated the formation of adherens junctions, concomitant with increased protein levels of E-cadherin and α-catenin. Furthermore, inhibition of RhoA or silencing of RhoA expression with siRNA increased the levels of E-cadherin and α-catenin. Inhibition of Rho kinases (ROCK), the RhoA effector proteins, also increased levels of E-cadherin and α-catenin and stimulated formation of adherens junctions. The motility of HCA-7 cells was significantly decreased when COX-2 or RhoA was inhibited. Therefore, our data reveal a novel molecular mechanism that links COX-2 signaling to disrupt the formation of adherens junctions; COX-2 stimulates the RhoA/ROCK pathway, which reduces levels of E-cadherin and α-catenin leading to disruption of adherens junction formation and increased motility. Understanding of COX-2 downstream signaling pathways that promote tumor progression is crucial for the development of novel therapeutic strategies. (Cancer Res 2006; 66(24): 11700-8)
Dimethylfumarate Impairs Melanoma Growth and Metastasis
Authors: Loewe Robert , Valero Teresa , Kremling Silvia , Pratscher Barbara , Kunstfeld Rainer , Pehamberger Hubert , Petzelbauer Peter
Published: December 2006

Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To identify targets of DMF action, we analyzed mRNA expression in DMF-treated melanomas by gene chip arrays. Using BiblioSphere software for data analysis, significantly regulated genes were mapped to Gene Ontology terms cell death, cell growth, and cell cycle. Indeed, we found that DMF inhibited proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle was arrested at the G2-M boundary. Moreover, DMF was proapoptotic, as shown by cell cycle analysis and by Annexin V and Apo2.7 staining. These results were confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by Ki-67 immunostaining and increased apoptosis as assessed by terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling staining. In conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth and metastasis in animal models. (Cancer Res 2006; 66(24): 11888-96)
Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies
Authors: Horsman Michael R. , Siemann Dietmar W.
Published: December 2006

A functional vascular supply is critical for the continued growth and development of solid tumors. It also plays a major role in metastatic spread of tumor cells. This importance has led to the concept of targeting the vasculature of the tumor as a form of cancer therapy. Two major types of vascular-targeting agent (VTA) have now emerged: those that prevent the angiogenic development of the neovasculature of the tumor and those that specifically damage the already established tumor vascular supply. When used alone neither approach readily leads to tumor control, and so, for VTAs to be most successful in the clinic they will need to be combined with more conventional therapies. However, by affecting the tumor vascular supply, these VTAs should induce pathophysiologic changes in variables, such as blood flow, pH, and oxygenation. Such changes could have negative or positive influences on the tumor response to more conventional therapies. This review aims to discuss the pathophysiologic changes induced by VTAs and the implications of these effects on the potential use of VTAs in combined modality therapy. (Cancer Res 2006; 66(24): 11520-39)
Human Kallikrein 8 Protease Confers a Favorable Clinical Outcome in Non–Small Cell Lung Cancer by Suppressing Tumor Cell Invasiveness
Authors: Sher Yuh-Pyng , Chou Cheng-Chung , Chou Ruey-Hwang , Wu Han-Ming , Wayne Chang Wun-Shaing , Chen Chun-Houh , Yang Pan-Chyr , Wu Cheng-Wen , Yu Chia-Li , Peck Konan
Published: December 2006

The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene family, encodes a serine protease. The KLK8 protein (hK8) is known to be a favorable prognostic marker in ovarian cancer, but the biological basis of this is not understood. We found that overexpressing the KLK8 gene in highly invasive lung cancer cell lines suppresses their invasiveness. This role in invasiveness was further confirmed by the fact that inhibition of endogenous KLK8 expression with a specific short hairpin RNA reduced cancer cell invasiveness. In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin. DNA microarray experiments and staining of cells for actin filaments revealed that the degradation of fibronectin by hK8 suppresses integrin signaling and retards cancer cell motility by inhibiting actin polymerization. In addition, studies in a mouse model coupled with the detection of circulating tumor cells by quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor growth and invasion in vivo. Finally, studies of clinical specimens from patients with non–small cell lung cancer showed that the time to postoperative recurrence was longer for early-stage patients (stages I and II) with high KLK8 expression (mean, 49.9 months) than for patients with low KLK8 expression (mean, 22.9 months). Collectively, these findings show that KLK8 expression confers a favorable clinical outcome in non–small cell lung cancer by suppressing tumor cell invasiveness. (Cancer Res 2006; 66(24): 11763-70)
A Review of Predictability Studies of Atlantic Sector Climate on Decadal Time Scales
Authors: Latif M. , Collins M. , Pohlmann H. , Keenlyside N.
Published: December 2006

This review paper discusses the physical basis and the potential for decadal climate predictability over the Atlantic and its adjacent land areas. Many observational and modeling studies describe pronounced decadal and multidecadal variability in the Atlantic Ocean. However, it still needs to be quantified to which extent the variations in the ocean drive variations in the atmosphere and over land. In particular, although a clear impact of the Tropics on the midlatitudes has been demonstrated, it is unclear if and how the extratropical atmosphere responds to midlatitudinal sea surface temperature anomalies.

Although the mechanisms behind the decadal to multidecadal variability in the Atlantic sector are still controversial, there is some consensus that some of the longer-term multidecadal variability is driven by variations in the thermohaline circulation. The variations in the North Atlantic thermohaline circulation appear to be predictable one to two decades ahead, as shown by a number of perfect model predictability experiments. The next few decades will be dominated by these multidecadal variations, although the effects of anthropogenic climate change are likely to introduce trends. Some impact of the variations of the thermohaline circulation on the atmosphere has been demonstrated in some studies so that useful decadal predictions with economic benefit may be possible.