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ScienceWeek
SCIENCE-WEEK
A Weekly Digest of the News of Science
July 10, 1998
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Our loyalties are to the species and the planet.
We speak for Earth. Our obligation to survive is
owed not just to ourselves but also to that Cosmos,
ancient and vast, from which we spring.
-- Carl Sagan (1934-1996)
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Contents of This Issue:
1. On Planetary Rings
2. On the Single-Atom Laser
3. Construction of Plant Cell Walls: A Geometrical Model
4. Motor Proteins: Dynein Arms as Force Generators
5. Papillomavirus and Cancer: Role of a Protein Polymorphism
6. Crystal Structure of an HIV Protein-Receptor-Antibody Complex
7. Neuron Interactions: Drivers vs. Modulators
8. Human Neurobiology: Split-Brain Research
9. Concern Over World Increase in Obesity Prevalence
10. Social Stress and Reactivation of Latent Herpes Simplex Virus
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1. ON PLANETARY RINGS
In little more than a decade, it will be 400 years since the
discovery by Galileo of the rings of Saturn, and the development
of our understanding of these rings, and of the rings of the
other outer planets, provides a cogent illustration of how the
knowledge of any epoch is constrained by the technology available
to science. The rings of Saturn, which are now known to number in
the thousands, extend over 100,000 kilometers from the surface of
the planet and have an unknown origin. At present, the apparent
best hypothesis is that the material in Saturn's rings is debris
from an icy moon of approximately 100 kilometers in diameter that
was shattered by the impact of a comet. ... ... In an essay on
the rings of Saturn and other planets, Neil F. Comins (University
of Maine, US) makes the following points: 1) In 1610, when
Galileo first discovered the rings of Saturn, the optics of his
instrument were so poor that he interpreted the rings as part of
a triple system consisting of two small bodies and the larger
planet. 2) In 1659, using better optics, Christiaan Huygens
discovered that the two smaller bodies were actually a ring,
described by Huygens as a single smooth ribbon circling the
planet. 3) In 1675, Giovanni Cassini observed the first feature
in the rings, the dark gap now known as Cassini's division. Since
the planet was visible through this gap, this was the first
inkling that the rings were not solid. 4) During the first half
of the 19th century, three concentric rings containing several
divisions were recognized, and the entire assembly of rings was
still a puzzle. 5) In 1857, the physicist James Clerk Maxwell,
first proposed that the rings of Saturn consist of countless
small pieces of matter. 6) In the latter part of the 19th
century, theoretical arguments established that the rings could
not be solid, that such solid rings could not assemble, and that
if a solid ring did assemble, there would be no way to hold it
together consistent with the known laws of gravity and mechanics.
7) In 1980 and 1981, the Voyager 1 and 2 spacecrafts confirmed
Maxwell's prediction that Saturn's rings are composed of small
pieces, and revealed that the rings are composed of thousands of
ringlets each only a few miles wide. 8) Parallel to these
discoveries concerning the rings of Saturn, the rings of Uranus
were discovered in 1977, the rings of Jupiter in 1979, and the
rings of Neptune in 1984. 9) Planetary rings appear permanent,
but in fact they decay in less than 100 million years unless they
are replenished. 10) Ringlets vary in brightness because each is
a different size and with different compositions. Brighter rings
are made mostly of ice or ice-covered rock, and particles can be
as small as sand grains and as large as 50 meters. 11) Neptune's
moon Triton orbits Neptune in a direction opposite to the
rotation of Neptune, which means that Triton will eventually slow
in orbit and begin a spiral toward the planet. When Triton falls
below the *Roche limit, the moon Triton (diameter 2705
kilometers) will disintegrate into a 35,000 kilometer band of
rubble above Neptune, and the debris will spread out into the
most massive and extensive ring in the solar system. But recent
calculations indicate the Triton breakup will not occur for
another billion years.
QY: Neil F. Comins, University of Maine 207-581-1110
(Astronomy July 1998) (Science-Week 10 Jul 98)
... ... *Roche limit: Named after the astronomer Edouard Roche
(1820-1883), who first formulated the quantitative expression,
this is the minimum distance from the center of a body at which a
satellite can remain in equilibrium under the influence of its
own gravitation and that of its host. Inside the Roche limit, a
satellite is torn apart by tidal forces. The Roche limit is not
fixed, but depends on the forces holding the satellite together,
its density, the density of the host, etc. Assuming the satellite
is held together only by gravitational attraction (zero tensile
strength) and has the same density as the host, the Roche limit
is approximately 2.45 times the radius of the host.
2. ON THE SINGLE-ATOM LASER
In general, resonance is a marked increase in the oscillation
amplitude of a system when the system is subjected to an
oscillating force whose frequency is the same or close to the
natural frequency of the system as determined by the system
parameters. The phenomenon occurs in all systems, including
optical systems. Coherent light waves are light waves of similar
phase, direction, and amplitude, and a laser (light amplification
by stimulated emission of radiation) is a device that converts
input power into a very narrow intense beam of coherent visible
or infrared light, the conversion mechanism essentially involving
excitation of atoms to a higher energy state producing resonator-
forced in-phase radiation. The power output of lasers depends on
the physical constraints, the number of excited entities
involved, the types of entities involved, etc., and the possible
power output ranges over a large spectrum. For example, the
neodymium-YAG laser (neodymium-yttrium-aluminum-garnet laser) has
a power output of the order of 1 watt and is useful for surgery;
the helium neon laser has a power output of the order 10^(-3)
watts and is used in such devices as bar-code scanners; the
microcavity semiconductor laser has a power output of the order
of 10^(-4) watts and is expected to have applications in future
optical computers now in the developmental stage; the singe-atom
laser has a power output of the order of 10^(-11) watts and is
primarily an experimental tool, but it may also find applications
in low-noise information processing and precision
spectroscopy.... ... Feld and An (2 installations, US KR) review
their own work on the single-atom laser and make the following
points: 1) The light generated by the single-atom laser exhibits
properties that can be explained only by quantum mechanics, and
it can be used to test the predictions of quantum theory and to
gain new insight into the nature of laser light. 2) The basis of
the single-atom laser device used by the authors is the process
known as quantized Rabi oscillation. The physicist I.I. Rabi
(1898-1988) studied in the 1930s the periodic exchange of energy
between atoms and an electromagnetic field (e.g., radio waves),
and the process came to be called "Rabi oscillation". In free
space, an excited atom will spontaneously emit a photon in a
random direction. In a resonant cavity, the temporal character-
istics of the emission are altered, a process known as "vacuum
Rabi oscillation", and if another excited atom enters the cavity
to be affected by the emitted photon from the first atom, the
process known as "quantized Rabi oscillation" occurs, and the
second atom emits an identical photon in the same direction as
the first but at a faster rate. [Editor's note: All of these
events are occurring within the domain of quantum electro-
dynamics, and brief verbal descriptions of the events without the
relevant defining equations are seriously handicapped.] In their
review, the authors outline part of their program for future
experiments, and they conclude that the single-atom laser may
assist in the future development of semiconductor lasers by
improving our understanding of quantum-mechanical phenomena.
QY: Michael S. Feld, Mass. Inst. of Technology 617-253-1000.
(Scientific American July 1998) (Science-Week 10 Jul 98)
3. CONSTRUCTION OF PLANT CELL WALLS: A GEOMETRICAL MODEL
Cell wall deposition is a key process in the formation, growth,
and differentiation of plant cells. The most important structural
components of the wall are long cellulose "microfibrils" that are
synthesized by special enzymes (synthases) embedded in the plasma
membrane of the plant cell. The microfibrils in higher plants are
made of cellulose, the most abundant macromolecule on Earth. They
are long (>> 1 micron) and thin (3-4 nanometers), and in the cell
wall, they are linked to wall matrix molecules excreted into the
wall by *exocytosis. A fundamental question is how the
microfibrils become oriented during deposition at the plasma
membrane. The current textbook explanation for the orientation
mechanism is a guidance system mediated by so-called cortical
*microtubules, but there too many apparent exceptions,
particularly in the case of the helicoidal arrangements that
occur in many systems. An additional construction mechanism that
has been proposed involves liquid crystalline self-assembly, but
the required amount of bulk material able to equilibrate
thermally is not normally present at any stage of the wall
deposition process. ... ... Emons and Mulder (2 installations,
NL) present a report in which they pose the question of whether
the complex ordered structure of helicoidal cell walls can be
formed in the absence of direct cellular guidance mechanisms.
They propose that such walls can indeed be formed by a mechanism
based on geometrical considerations. The most important
geometrical constraint in this model is stated by the authors as
follows: "Given the space-limiting conditions and the absence of
gaps in the microfibril pattern, the deposition process can be
viewed as analogous to winding strings around a cylinder in such
a way that its surface is fully covered. Therefore, a simple
geometrical rule must link the number of strings being wound
simultaneously per cell circumference to the angle they make with
a plane perpendicular to the cell axis." The authors suggest
their model explains the genesis of the complicated helicoidal
texture, and that the model indicates the cell has intrinsic,
versatile tools for creating a variety of textures. The authors
further suggest that a compelling feature of their model is that
"local rules generate global order, a typical phenomenon of
life."
QY: Anne Mie C. Emons (annemie.emons@algem.pcm.wau.nl)
(Proc. Natl. Acad. Sci. US 9 Jun 98 95:7215)
(Science-Week 10 Jul 98)
-------------------
Related Background:
... ... *exocytosis: This refers to the bulk transport of
materials out of the cell across the cell membrane (plasma
membrane). The process generally involves the encasing of the
material within intracellular membranes, forming a "vacuole", and
the subsequent transport of the vacuole to the cell surface. At
the cell surface, the vacuole fuses with the plasma membrane, and
the contents of the vacuole are deposited outside the cell.
Various aspects of the process are visible with both light and
electron microscopy in a variety of cell systems, and this is the
process primarily responsible for excretion and secretion by
individual cells.
... ... *microtubules: Composed of the protein tubulin,
microtubules are part of the cytoskeleton of biological cells,
the quasi-rigid matrix that among other things determines cell
shape. The microtubules are 25 nanometers in diameter and occur
in regular arrays. Cortical microtubules are microtubules
structuring the surfaces of cells.
4. MOTOR PROTEINS: DYNEIN ARMS AS FORCE GENERATORS
"Motor proteins" are mechanico-chemical enzymes involved in
locomotion of cells or transport of materials in cells, and there
are three families of such proteins: kinesins, dyneins, and
myosins. Kinesins and dyneins are microtubule based motor
proteins, while myosin is a microfilament based motor protein. In
general, as mechanico-chemical enzymes, motor proteins convert
energy from hydrolysis of nucleotides to mechanical force, and
since they are involved in many important cellular events, the
molecular details are currently the focus of intensive research.
Many eukaryotic cells (cells that have membrane-bound organelles
such as a cell nucleus) have flagella, long whip-like structures,
that beat rhythmically. The central core of the flagellum is
called the "axoneme", and it consists of a regular array of
microtubules (see background material in previous report). The
motor protein dynein is known to power flagellar motion,
suggesting that oscillation may be inherent in this protein.
... ... Shingyoji et al (5 authors at 4 installations, JP)
report an attempt to determine whether oscillation is a property
of dynein arms themselves, or whether oscillation requires an
intact axoneme. Using *optical trapping nanometry, the authors
measured the force generated by a few dynein arms on an isolated
doublet microtubule. When the dynein arms on the doublet
microtubule contact a singlet microtubule and are activated by
photolysis of adenosine triphosphate (ATP), they generate a
force that moves the singlet microtubule over the perpendicular
doublet in a processive manner, the force and displacement in
oscillation, with the maximum frequency of the oscillation
dependent on ATP concentration. The authors suggest that
oscillation of dynein arms may be a basic mechanism underlying
flagellar beating, and that their results may be important not
only for understanding the mechanism of flagellar beating, but
also for understanding the functions of motor proteins in
general.
QY: Chikako Shingyoji (chikako@biol.s.u-tokyo.ac.jp)
(Nature 18 Jun 98 393:711) (Science-Week 10 Jul 98)
-------------------
Related Background:
... ... *optical trapping nanometry: The term "optical trapping"
refers to the confinement of (microscale) entities in a
restricted geometry by the controlled action of (laser) light,
and optical trapping nanometry is a method of making nanoscale
measurements of such entities. In this experiment, the optically
trapped entity is a fluorescent bead (1 micron diameter)
crosslinked with the biotin of the singlet microtubule, the
method allowing measurement of the nanoscale displacements of the
bead-microtubule entity as it is moved by the underlying doublet
dynein arms.
-------------------
Related Background:
DETAILS OF DYNEIN MOTOR DOMAIN MECHANISMS
... Gee et al (3 authors at 3 installations, US) report that the
entire carboxy-terminal two-thirds of the 532K dalton force-
producing heavy chain subunit of dynein is required for ATP-
binding activity. They have also identified a distal microtubule-
binding domain that apparently forms a hairpin-like stalk. The
authors suggest the mechanism for dynein force production differs
substantially from that of other motor proteins.
QY: Richard B. Vallee
(Nature 11 Dec 97) (Science-Week 2 Jan 98)
5. PAPILLOMAVIRUS AND CANCER: ROLE OF A PROTEIN POLYMORPHISM
Human cells have a suicide program that is triggered by a
protein (p53) when the cell's genetic machinery is damaged. Some
viruses possess a gene that inactivates the protein p53, which
enables them to use the cell's genetic apparatus to reproduce,
with the eventual death of the host cell. A genetic polymorphism
is a naturally occurring variation in the normal nucleotide
sequence of the genome within individuals in a population, and an
allele is one of two or more forms of a given gene that control a
particular characteristic, with the alternative forms occupying
corresponding loci on homologous chromosomes. Variations are
denoted as polymorphisms only if they cannot be accounted for by
recurrent mutation and occur with a frequency of at least about
1%. In general, perverse polymorphisms (as opposed to benign
polymorphisms) are genetic variations that are linked to
pathological processes. Genital warts are caused by human
papillomaviruses (HPVs) of various types (e.g., HPV types 1, 2,
6, 11, 16, 18), and such infections by certain types of the virus
have been linked to various cancers, in particular to carcinoma
of the uterine cervix, the 2nd most common malignancy of the
female reproductive tract (virus types 16 and 18, denoted as HPV-
16 and HPV-18)). HPV-16 and HPV-18 encode two major oncoproteins
(cancer-inducing proteins), E6 and E7. The E7 protein binds to
and inactivates the cellular tumor-suppressor protein Rb, while
the E6 protein binds to the cellular tumor-suppressor protein p53
and directs its metabolic degradation. ... ... Storey et al (10
authors at 4 installations, UK IT CA) report a study of the role
of a p53 protein polymorphism in the development of human
papillomavirus-associated cancer. A common polymorphism that
occurs in the p53 amino-acid sequence results in the presence of
either a proline or an arginine at position 72. The authors
investigated the effect of this polymorphism on the suscept-
ibility of p53 to E6-mediated degradation, and the arginine form
of p53 was found to be significantly more susceptible than the
proline form. Analysis of genetic material from patients with
human papillomavirus associated tumors revealed a striking
overrepresentation of the arginine p53 polymorphism compared with
the normal population, with a cancerous-tumor risk factor in the
arginine p53 polymorphism group 7 times that of the proline p53
group. The authors suggest the arginine allele therefore
represents a significant risk factor in the development of human
papillomavirus-associated cancers, and that epidemiological
surveys should be undertaken in larger populations and in
different geographical regions to determine the role of this p53
polymorphism in human papillomavirus-associated lesions, human
papillomavirus infection, and the development of premalignant
lesions where infection has been established.
QY: Lawrence Banks, International Centre for Genetic Engineering
and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
(Nature 21 May 98 393:229) (Science-Week 10 Jul 98)
6. CRYSTAL STRUCTURE OF AN HIV PROTEIN-RECEPTOR-ANTIBODY COMPLEX
The human immunodeficiency viruses *HIV-1 and *HIV-2 and the
related simian immunodeficiency virus (SIV) cause the destruction
of *lymphocytes with expressed *CD4 surface receptors (CD4+
lymphocytes) in their respective hosts, resulting in the
development of acquired immunodeficiency syndrome (AIDS). The
entry of HIV into host cells requires the sequential interaction
of the viral exterior envelope glycoprotein gp120 with the CD4
glycoprotein and a *chemokine receptor on the host cell surface.
These interactions initiate a fusion of the viral and cellular
membranes. Although gp120 protein can elicit virus-neutralizing
*antibodies, HIV manages to elude the defenses of the host immune
system. ... ... Kwong et al (6 authors at 4 installations, US)
report the determination of the x-ray crystal structure at 2.5
angstrom resolution of an HIV-1 gp120 core complexed with a
fragment of human CD4 and an antigen-binding fragment of a
neutralizing antibody that blocks chemokine-receptor binding. The
crystal structure reveals a cavity-laden CD4-gp120 interface, a
conserved binding site for the chemokine receptor, evidence for a
conformational change upon CD4 binding, and indications for
specific mechanisms enabling immune system evasion by the virus.
The authors suggest their results provide a framework for
understanding the complex biology of HIV entry into cells and
should guide efforts at intervention in the pathological process.
QY: Wayne A. Hendrickson (wayne@convex.hhmi.columbia.edu)
(Nature 18 Jun 98 393:648) (Science-Week 10 Jul 98)
-------------------
Related Background:
... ... *HIV-1 and *HIV-2: HIV-1 is the subtype of HIV that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV-2 is the principal agent of
AIDS in West Africa.
... ... *lymphocytes: Lymphocytes are a type of leukocyte
responsible for the immune response. There are two classes of
lymphocytes: 1) the B-cells, when presented with a foreign
chemical entity (antigen), change into antibody producing plasma
cells; and, 2) the T-cells interact directly with foreign
invaders such as bacteria and viruses.
... ... *antibodies: An antibody is a protein molecule produced
by the immune system of vertebrate organisms, the molecule
designed to specifically interact with a particular invading
foreign chemical entity called an antigen.
... ... *CD4: CD4 is a protein "marker" on the surfaces of so-
called helper T-cells of the immune system. The T-cells derive
their name from the thymus gland, the organ in which they mature.
... ... *chemokine receptor: Chemokines are immune system
signaling molecules; the receptors for chemokines are proteins on
the surfaces of cells.
-------------------
Related Background:
AN HIV PROTEIN THAT PROTECTS THE HOST CELL AGAINST T-CELLS
T-cells are small circulating lymphocytes arising in bone marrow
and maturing into various subtypes in the thymus or as a result
of exposure to a hormone released by the thymus. The T-cells have
a variety of involvements, including the cellular immune
responses, graft rejection, and delay of allergic reactions.
Helper T-cells provoke the production of antibodies by B-cells of
the immune system. Cytotoxic T-cells lyse (kill by rupturing:
lysis) virus-infected cells. The virus called HIV (human immune
deficiency virus) exhibits great specificity for the helper
T-cells of the human immune system, and HIV-1 is the subtype of
HIV that causes most cases of AIDS in the Western Hemisphere,
Europe, and Central, South, and East Africa. The term "epitope"
refers to the region of an antigen molecule responsible for its
specificity in an antigen-antibody interaction: the epitope is
recognized by the antigen-binding site of a specific antibody
molecule. The term "viral epitope", in the context of this
report, refers to a viral-origin epitope that is expressed on the
surface of virus-infected host cells. ... ... Collins et al (5
authors at 5 installations, US) report a study of the ability of
cytotoxic T-cells to recognize and kill HIV-1 infected primary T-
cells, and that cytotoxic T-cells inefficiently lysed infected
primary cells if the viral gene protein product (Nef) was
expressed. The authors suggest that the protein Nef protects HIV-
1 infected cells by reducing the viral epitope on their
surfaces.
QY: David Baltimore
(Nature 22 Jan 98) (Science-Week 6 Feb 98)
-------------------
Related Background:
EVIDENCE THAT CYTOMEGALOVIRUS ASSISTS HIV INFECTION
There is intense interest among virologists in chemokines, which
are immune system signaling molecules. The receptors for
chemokines are proteins on the surfaces of cells, and there is
evidence that HIV uses these receptors to force entry into cells.
Now there is new evidence that cytomegalovirus (CMV), a rather
ubiquitous viral entity, may, upon successful invasion of cells,
force the production of a cell surface chemokine receptor protein
called US28, and that US28, in turn, may act as a docking and
membrane fusion locus for HIV. The results were reported by
Olivier Pleskoff et al (Institut Cochin de Genetique Moleculaire,
FR; University of Paris, FR). Up to 80% of the general
population, and almost all HIV-infected homosexual males, are
known to be infected with CMV. If these results are correct, then
virologists will need to shift their thinking to include the
possibility of direct cooperative interaction between different
viral pathogens. (Science 20 Jun 97) (Science-Week 26 Jun 97)
7. NEURON INTERACTIONS: DRIVERS VS. MODULATORS
When one nerve cell transmits signals to another nerve cell, its
*postsynaptic effect can vary greatly. In sensory systems, inputs
from "drivers" can be differentiated from those of "modulators".
The driver can be identified as the transmitter of *receptive
field properties; the modulator can be identified as a neuron
that alters the probability of certain aspects of that
transmission. Where receptive fields are not involved, the
distinction is more difficult and currently is undefined.
... ... Sherman and Guillery (2 installations, US) present an
analysis of the ways in which drivers can be distinguished from
modulators in the visual pathway, in particular in the *thalamic
geniculate relay, a system for which much relevant
electrophysiological evidence is available. The authors also
consider the extent to which the distinction between driver and
modulator may apply to other parts of the thalamus and to other
parts of the brain. They suggest the following distinctions: 1)
Driver input-output correlation diagrams have sharper peaks than
those from modulators. 2) There are likely to be few drivers but
many modulators for any one postsynaptic neuron. 3) Drivers are
likely to act only through *ionotropic receptors having a fast
postsynaptic effect, whereas modulators also are likely to
activate *metabotropic receptors having a slow and prolonged
postsynaptic effect.
QY: S. Murray Sherman (ssherman@neurobio.sunysb.edu)
(Proc. Natl. Acad. Sci. US 9 Jun 98 95:7121)
(Science-Week 10 Jul 98)
-------------------
Related Background:
That the nervous system has evolved as an information
transmission system is perhaps most clearly seen in the anatomy
and physiology of those parts of the nervous system involved in
relaying information about the outside world to central
processing "stations". There are enormous number of neural
entities involved in such transmissions, but the basic paradigm
at the unit level is ubiquitous: information travels upstream
(with several important feedback mechanisms), the information
transmitted by input neurons (presynaptic neurons) to the
junction between neurons (the synapse) to the output neuron (the
postsynaptic neuron). The peripheral receptor cells in contact
with the external world are usually organized in a surface (e.g.,
visual, auditory, touch receptors), and the information that is
transmitted to the brain concerns which points in this "receptive
field" have been activated by interaction with external physical
events (light, vibration, punctile mechanical contact, etc.). In
the visual system of mammals, information from the retina is sent
to a part of the brain called the "thalamus", where it provides
the input to a collection of nerve cells (a "nucleus") called the
lateral geniculate nucleus, and the neurons in this nucleus in
turn send information to the part of the brain responsible for
analysis of visual information (visual cortex). The receptive
field at the periphery, in essence, is "mapped" and transmitted
to a higher-level analytical station.
... ... *postsynaptic: In general, this term applies to any event
occurring on the "output" side of the junction between nerve
cells.
... ... *receptive field: The 2-dimensional (usually) peripheral
sensory representation of physical input from the environment.
... ... *thalamic geniculate relay: Refers to relaying of
peripheral visual information, the pathway: retina > thalamus >
cerebral cortex.
... ... *ionotropic receptors: Receptors whose activation by
specific ligands alters various ion permeabilities that control
the electrical activity of the nerve cell.
... ... *metabotropic receptors: Receptors whose activation by
specific ligands alters the metabolism of the nerve cell (which,
among other things, may have long-term effects on ion
permeabilities).
-------------------
Related Background:
SYNCHRONIZATION AND RATE MODULATION IN MOTOR CORTEX NEURONS
Cognitive motor processes are task-oriented behaviors involving
voluntary muscle movements, for example, the deliberate reaching
out for and lifting of an object in response to a stimulus. In
the mammalian brain, the primary motor cortex is the area of the
cerebral cortex containing nerve cells and neural circuits
responsible for voluntary movement, the signaling to peripheral
muscles involving the propagation of electrical changes (action
potentials) the length of long nerve fibers from the brain to the
spinal cord. The neurons of the motor cortex are themselves
responding to inputs of action potentials from neurons elsewhere
in the brain, so the output of the motor cortex is a result of
complex interactions of neurons within the motor cortex and of
these neurons with neurons outside the motor cortex. Since it is
possible to fix electrodes in the motor cortex and record the
local electrical activity of nerve cells in that region, there
has been extensive research to delineate the interactions between
motor cortex neurons and the relation of these interactions to
behavior. Two important parameters in this context are the
discharge rate of action potentials by neurons and the degree of
synchronization of activity of connected nerve cells. Riehle et
al (4 authors at 3 installations, FR IL DE) report that simultan-
eous recording of neuron activity in primary motor cortex of
monkeys during task performance reveals context dependent rapid
changes in patterns of coincident action potentials. Spike
synchronization and discharge rate modulations occur in relation
to external events, but the latter are not precisely time-locked.
Spike synchronization also occurs in relation to internal events
(stimulus expectancy) where firing rate modulations are absent.
The authors suggest their findings indicate that internally
generated synchronization of individual spike discharges may be
involved in the cortical organization of cognitive motor
processes. QY: Alexa Riehle
(Science 12 Dec 97) (Science-Week 2 Jan 98)
-------------------
Related Background:
RETROGRADE AND ANTEROGRADE CONDUCTION IN NEURON DENDRITES
Nerve cells, in biological systems which have nerve cells, come
in all shapes and sizes, with the various shapes and sizes
correlated or not yet correlated with various functions. The
generalized neuron is more or less modeled after the vertebrate
motor neuron, a nerve cell with a particular morphology and a
particular relation of its morphology to its function, but all
neurobiologists are aware of the multiplicities of nerve cell
design actually found in nature, and the multiplicities of the
way various types of nerve cell behave. In the classical
generalized neuron, the idea is that the various membrane
depolarizations and hyperpolarizations that are the inputs to the
neuron are summated as excitatory and inhibitory inputs with an
end result at the initial segment of the axon hillock just beyond
the cell body that determines whether the nerve cell fires an
action potential that will be propagated along its axon to
another neuron or to a muscle cell. This paradigm is the classic
paradigm, supremely useful as a conceptual scheme (and a scheme
that produced at least 4 Nobel Prizes), but the fact is many
neuron types, particularly in the vertebrate brain, are
exceptions to the generalization. This may be particularly true
of the dendritic arborizations of central nervous system neurons,
and one of the fundamental questions of neurobiology is to
unravel the electrophysiology of nerve cell dendrites, and in
particular to determine if and when dendrites of particular types
of neurons actually conduct action potentials. Now Wei R. Chen et
al (3 authors at 2 installations, US, DK) report that electro-
physiological observations of the rat olfactory mitral nerve cell
indicate that the action potential can be initiated either in the
soma-axon hillock or in the distal primary dendrite, and that the
initiation site is controlled by excitatory synaptic inputs to
the distal dendrite and inhibitory synaptic inputs near the cell
body. The authors suggest that mitral cells provide a model that
widens the view of how dendritic excitability contributes to
information processing in different types of neurons in the
vertebrate brain.
QY: W. R. Chen, Yale Univ. School of Medicine, Neurobiol. (203)
785-2644.
(Science 17 Oct 1997) (Science-Week 7 Nov 97)
-------------------
Related Background:
AN ANALYSIS OF ACTION POTENTIAL DYNAMICS AT NEURON TERMINALS
The classical view of the electrical activity of nerve cells
divides the neuron into parts and specifies what types of
electrical activity the various parts of the nerve cell can
exhibit. Thus, the classical view was that axons conduct action
potentials and cell bodies receive input from other neurons and
integrate this input to produce an electrical effect on the
initial segment of the axon, the part of the axon that emerges
from the cell body. Nerve cells, however, are complicated cells
with various morphologies and functions, and even in the same
organism the simple view is only a basis from which variations
diverge. The fine terminals of axons in invertebrates, for
example, are places where presynaptic interactions with other
neurons are known to occur. Dominique Debanne et al (Brain
Research Institute, Zurich CH) have investigated the electrical
activity of pairs of pyramidal cells in rat hippocampal slice
cultures, and have observed that propagation of action potentials
to nerve terminals is impaired if presynaptic potentials are
preceded by either brief or tonic hyperpolarization. The authors
conclude that these axons do not always behave as simple
electrical cables, but their capacity to transmit action
potentials may be determined by a time-dependent integration of
preceding changes in membrane potential, with the state of the
I(A) potassium conductance channel apparently of considerable
importance to the process.
QY: D. Debanne
(Nature 18 Sep 97) (Science-Week 3 Oct 97)
8. HUMAN NEUROBIOLOGY: SPLIT-BRAIN RESEARCH
The human nervous system (and the nervous systems of many other
vertebrate species) has a bilateral symmetry most noticeable in
the existence of the two cerebral hemispheres. The two halves of
the brain, although exhibiting certain functional specializat-
ions, ordinarily work in an integrated manner to produce the
conscious output of the nervous system, namely thought and
action. Epilepsy is the general name given to a class of nervous
system disorders involving convulsive activity of large numbers
of nerve cells, and a classical surgical procedure in cases of
severe epilepsy is section of the corpus callosum, the large band
of nerve fibers that serves as the primary connection between the
two halves of the brain. More than 30 years ago, Roger W. Sperry
(1913-1994) and his coworkers began a series of studies of
"split-brain" humans, patients who had had the corpus callosum
severed as a therapeutic procedure, and the observations of these
clinical patients have formed the basis for a number of signif-
icant ideas concerning brain function. ... ... Michael S.
Gazzaniga (Dartmouth College, US), a member of Sperry's original
group, presents a review of the history and current status of
human split-brain research, and makes the following points: 1) In
the classical split-brain patient, visual information no longer
moves between the two sides of the brain. If an image is
projected to the right visual field (i.e., to the left
hemisphere, which is where information to the right field is
processed) patients can describe what they see. But when the same
image is displayed to the left visual field (i.e., to the right
hemisphere), the patient cannot describe what they see. But if
the patient is asked to point to an object similar to the object
being projected, they do so with ease. The right brain sees the
image and can mobilize a nonverbal response, but it cannot talk
about what it sees. 2) The same situation obtains for touch,
smell, and sound. 3) Additionally, each half of the brain can
control the upper muscles of both arms, but the muscles
manipulating hand and finger movements can be orchestrated only
by the contralateral hemisphere. In other words, the right
hemisphere can control only the left hand and the left hemisphere
only the right hand. 4) Ultimately, it was discovered that the
two hemispheres control vastly different aspects of thought and
action. Each half of the brain has its own specialization, and
thus its own limitations and advantages. The left brain is
dominant for language and speech, the right brain excels at
visual-motor tasks. 5) During the past decades, research in
cognitive science, artificial intelligence, evolutionary
psychology, and neuroscience has directed attention to the idea
that brain and mind are built from discrete units -- or modules -
- that carry out specific functions. According to this theory,
the brain is not a general problem-solving device whose every
part is capable of any function. Rather it is a collection of
devices that assists the mind's information processing demands.
Gazzaniga concludes: "After many years of fascinating research on
the split brain, it appears that the inventive and interpreting
left hemisphere has a conscious experience very different from
that of the truthful, literal right brain. Although both
hemispheres can be viewed as conscious, the left brain's
consciousness far surpasses that of the right. Which raises
another set of questions that should keep us busy for the next 30
years or so."
QY: Michael S. Gazzaniga, Dartmouth College 603-646-2875.
(Scientific American July 1998) (Science-Week 10 Jul 98)
-------------------
Related Background:
ON MODULAR COGNITIVE SYSTEMS IN THE HUMAN BRAIN
One of the central challenges of cognitive neuroscience is to
unmask the apparent unitary nature of perceptual, memorial, and
cognitive systems. Neuropsychological analyses, functional brain-
imaging methods, and analyses of normal reaction times have
revealed that apparently unitary processes consist of multiple
components. Frequently, these multiple components are distributed
across the cerebral hemispheres, but appear unified because of
the integration possible via the corpus callosum.
... ... Baynes et al (4 authors at 3 installations, US) report a
case of elective surgery for a severe epileptic disorder, the
surgery involving a resection of the corpus callosum in a left-
handed woman with left-hemisphere dominance for spoken language.
The patient demonstrated a dissociation between spoken and
written language. Words flashed to the dominant left hemisphere
were easily spoken out loud, but could not be written. When words
were flashed to the patient's right hemisphere, she could not
speak them out loud but she could write them with her left hand.
The authors suggest this marked dissociation supports the view
that spoken and written language output can be controlled by
independent hemispheres, even if before hemispheric disconnection
spoken and written language appear as inseparable cognitive
entities.
QY: Kathleen Baynes (kbaynes@ucdavis.edu)
(Science 8 May 98 280:902) (Science-Week 29 May 98)
-------------------
Related Background:
BRAIN PLASTICITY IN CHILDREN AFTER HEMISPHERECTOMY
Epilepsy is a term unhappily applied to several dozen different
seizure disorders, their commonality being central nervous system
seizures rather than identical pathological processes causing the
seizures. From a neurophysiological standpoint, a seizure is the
end result of a massive discharge of nerve cells, often the motor
neuron pathways that activate muscle cells. Seizures can be
produced by various central nervous system infections, metabolic
disturbances, toxic agents, cerebral oxygen deficiency, expanding
brain lesions, cerebral trauma, cerebral hemorrhage, and so on.
In general, any physiological event or series of events that
produces a wide disruption of central nervous system activity has
the potential for production of seizures of one sort or another.
Most patients who for reasons known (symptomatic epilepsies) or
unknown (idiopathic epilepsies) are chronically subjected to
seizures can be helped with various pharmacological agents such
as phenytoin or cloneazepam, but 10% to 20% of patients have
seizures that cannot be managed by drugs. If the seizures are due
to a specific damaged locus in the brain (the "epileptic focus"),
the recourse for these patients, if the locus can be determined,
is surgery. What is done is to completely remove the epileptic
focus, sometimes an area no larger than a small coin, and if the
surgery is successful the cure is immediate and permanent. There
are cases, however, in which the affected part of the brain is
quite large, the seizures completely unmanageable, and the only
recourse is radical surgery. Since severe chronic epilepsy due to
brain lesions is usually first diagnosed in young children, it is
such children who are the usual patients in radical brain surgery
for epilepsy. The most radical and fairly common procedure is
hemispherectomy, removal of an entire half of the brain, and the
most remarkable aspect of this is that when the surgical
procedure is successful, not only are the seizures eliminated,
but the child can function as well or almost as well as any other
child. It is an example of a phenomenon well-known to neuro-
biologists called "brain plasticity", the ability of the brain to
recover the function of a damaged or removed region by assignment
of the function to an undamaged location. The language area of
the brain, for example, is often considered to be fixed on the
left side of the brain by genetics, but in truth it is not so
fixed, and if the left side of the brain is removed at an early
age, the right side of the brain will quickly develop a language
center and there will be little functional impairment. In a
recent publication, Eileen P. G. Vining (Johns Hopkins Univ-
ersity, Baltimore MD US) reports the progress of 54 children who
underwent hemispherectomy for recurrent severe epileptic
seizures. The majority of the patients were seizure-free
following surgery, no longer needed drugs, and many of the
patients are now in school. One of the most significant facts
about the human brain is that its histological development
continues at least until adolescence, and the dynamism of this
histological development is what is responsible for its
remarkable plasticity.
QY: E. Vining, Johns Hopkins University (410) 516-8171.
(Pediatrics August 1997)
9. CONCERN OVER WORLD INCREASE IN OBESITY PREVALENCE
Obesity, which is defined as the excessive accumulation of body
fat, has apparently become a problem of international concern.
The World Health Organization and the International Obesity Task
Force have declared "an obesity epidemic on a global scale." The
index used to assess obesity is the so-called Body-Mass Index,
defined as the ratio of weight in kilograms to height in meters
squared: W/M^(2). Clinical obesity is defined as a Body-Mass
Index greater than 30. At the present time, 22.5 percent of the
US population is considered to be clinically obese, compared to
only 14.5 percent in 1980. The increase is apparently seen in all
demographic groups, including children. Comparable increases have
been noted in the United Kingdom, Brazil, Canada, and Australia.
Although experts evidently agree the worldwide increase has been
substantial during the past 15 years, the cause remains a puzzle.
QY: Gary Taubes (science_editors@aaas.org)
(Science 29 May 98 280:1367) (Science-Week 10 Jul 98)
-------------------
Related Background:
OBESITY AND MORTALITY: SPINNING SCIENCE NEWS
Stevens et al (6 authors at 4 installations, US), in a study of
the mortality of 62,116 men and 262,019 women during a 12 year
period (1960-1972), report that excess body weight increases the
risk of death from any cause and from cardiovascular disease in
adults between 30 and 74 years of age, and that the relative risk
associated with greater body weight is higher among younger
subjects. The above words are essentially the exact conclusions
chosen to be published by the authors. Nevertheless, two variants
of contrary journalistic "spin" have appeared, an interesting
illustration of how public health news is formulated. In the
first variant, in an editorial in the same journal in which the
Stevens et al report appeared, two journal editors emphasize that
the mortality increase with body-mass is modest and age-depend-
ent, and they urge an end to people "suffering immeasurable
torment in fruitless weight-loss schemes and scams." In the
second variant, published by the New York Times and echoed by
many newspapers across the US, news items took note of the
journal editorial and went a step further in headlines suggesting
excess weight has now been shown to be harmless. The spin-logic
in the case of both the journal editors and the news media is
apparently that since the effect is small, the public can well
disregard it. The researchers and authors of the article,
however, apparently believe otherwise, and the last sentence of
their article is unequivocal: "In healthy white adults below the
age of 75 who have never smoked cigarettes, our results are
consistent with the healthy weight ranges proposed in the 1995
Dietary Guidelines for Americans." QY: June Stevens, Univ. of
North Carolina, Dept. of Epidemiology 919-966-7458
(New England J. Med. 1 Jan 98) (Science-Week 9 Jan 98)
-------------------
Related Background:
FIRST IDENTIFICATION OF MOUSE OBESITY GENE IN HUMANS
In 1994 an obesity gene and its protein product (leptin), were
discovered in obese mice. It has been determined that a defect in
the gene causes a severe reduction in the output of functional
leptin by fat cells (adipocytes). Leptin apparently acts as a
messenger to the hypothalamus in the brain, the absence of the
protein causing excessive eating behavior without satiation. Now
a similar gene has been discovered in humans, this gene also
responsible for the production of leptin by human adipocytes.
Carl T. Montague et al (15 authors at various installations, UK)
studied a homozygous genetic defect in two children suffering
from extreme obesity, and have isolated and characterized the
gene, and related it to the previously identified mouse gene
known as ob/ob. As in mice, the result of a defect in the gene is
an order of magnitude reduction in the circulating blood
concentration of the protein leptin. The results do not mean that
all instances of obesity in humans are produced by defects in
this gene, but certainly a new area of research into the
molecular genetics of human obesity has now been defined. In
addition, the authors offer the hope that recombinant human
leptin may be found to correct leptin deficiency in clinical
cases. (Nature 26 Jun 97) (Science-Week 3 Jul 97)
10. SOCIAL STRESS AND REACTIVATION OF LATENT HERPES SIMPLEX VIRUS
There is compelling evidence that the nervous, endocrine, and
immune systems communicate by means of a common biochemical
language. The sharing of ligands (hormones, neurotransmitters,
and *cytokines) and their receptors constitute a biochemical
information circuit between each of these systems to maintain
physiological *homeostasis. Good health, whether physical or
psychological is predicated on a highly integrated repertoire of
defensive responses against external pathogens and stimuli that
threaten homeostasis. Disruption of homeostasis, by engagement of
either the immune, nervous, or endocrine systems by an external
or internal stimulus, will alter the production of signaling
molecules in one system, resulting in the modulation of the other
systems. There are two types of herpes simplex virus (HSV), the
pathological processes they cause differentiated by the locus of
the symptoms (type 1, face; type 2, genitalia). Once resident in
the host body following the initial infection and symptoms, the
virus remains dormant in nerve ganglia (the "latent" stage), with
irregular herpetic eruptions appearing in response to various
stimuli. Psychological stress is thought to contribute to
reactivation of the virus. Although several animal models have
been developed in an effort to reproduce different pathogenic
aspects of HSV-1 infection (HSV keratitis or labialis), there has
been no good animal model in which application of a psychological
laboratory stressor results in reliable reactivation of the
virus. ... ... Padgett et al (6 authors at Ohio State University,
US) now report that disruption of the social hierarchy within
colonies of mice increases aggression among cohorts, activates
the hypothalamic-pituitary-adrenal axis, and causes reactivation
of latent HSV-1 in more than 40 percent of latently infected
animals. In contrast, activation of the hypothalamic-pituitary-
adrenal axis using restraint stress does not activate the latent
virus. The authors suggest that the use of social stress in mice
provides a good model in which to investigate the neuroendocrine
mechanisms that underlie behaviorally mediated reactivation of
latent herpesviruses.
QY: Ronald Glaser (glaser.1@osu.edu)
(Proc. Natl. Acad. Sci. US 9 June 98 95:7231)
(Science-Week 10 Jul 98)
-------------------
Related Background:
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Certain cytokines are endogenous,
and need to be controlled by cell regulatory mechanisms. When
these mechanisms fail, endogenous cytokines may be implicated in
serious human diseases such as rheumatoid arthritis, where
apparently deregulated cytokines cause the inflammatory response
that produces the symptoms. As a promoter of cell growth and
division, a cytokine acts as a messenger to cells, and the
transmission of the message requires a binding of the cytokine
molecule to a cytokine-specific receptor on the cell surface.
This receptor is either a protein or a protein complex or a part
of a protein.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body temper-
ature. Similar homeostatic mechanisms operate at cellular levels.
-------------------
Related Background:
FURTHER EVIDENCE OF HERPES VIRUS ROLE IN KAPOSI'S SARCOMA
Kaposi's sarcoma is a human cancer of skin cells (and sometimes
cells of certain internal tissues), appearing for the most part
in elderly men or in younger men with compromised immune systems.
The disease was first described by the Hungarian dermatologist
Moritz Kaposi (1837-1902). ... ... Martin et al (6 authors at 3
installations, US) report a study of human herpes virus type 8
(HHV-8). The prevalence of HHV-8 infection is high among
homosexual men, correlates with the number of homosexual
partners, and is temporally and independently associated with
Kaposi's sarcoma. The authors suggest their observations are
further evidence that HHV-8 has an etiological role in Kaposi's
sarcoma and is sexually transmitted among men, and that
understanding the epidemiology of HHV-8 is a critical first step
in designing interventions to decrease the transmission of this
pathogen.
QY: Dean H. Kedes, Univ. of Calif. San Francisco 415-476-4044.
(New England J. Med. 2 Apr 98) (Science-Week 10 Apr 98)
-------------------
Related Background:
HERPES VIRUS MOLECULAR MIMICRY AND AUTOIMMUNE DISEASE
An autoimmune disease is one of a large group of diseases
characterized by cells of the immune system attacking other cells
of the body, in effect failing to recognize these other cells as
"friendly". Antigens are chemical moieties, often proteins, that
provoke immune responses, and the "epitope" is the small region
of the antigen apparently involved in binding or recognition of
the antigen. T-cells, of which there are various types, are
aggressive immune system cells, first formed in bone marrow, then
maturing in the thymus gland [hence: T(hymus)-cell]. A keratitis
is an inflammation of the cornea, and stromal keratitis is an
inflammation of the connective tissue framework of the cornea.
Invasion of the corneal stroma by herpes simplex virus is one of
the possible consequences of herpes simplex infection. Viral
infection is sometimes associated with the initiation or exacer-
bation of autoimmune disease, although the underlying mechanisms
have been unclear. One proposed mechanism is that viral chemical
moieties that mimic host antigens trigger certain T-cells to
destroy host tissue. ... ... Zhao et al (5 authors at 2 install-
ations, US) report that an epitope of a coat protein of herpes
simplex virus type 1 (KOS strain) is recognized by autoreactive
T-cells that target corneal antigens in a mouse model of auto-
immune herpes stromal keratitis. Mutant viruses that lacked this
epitope did not induce autoimmune disease. The authors suggest
that expression of molecular mimics can influence the development
of autoimmune disease after viral infection. QY: Zi-Shan Zhao,
Dept. of Pathology, Harvard Univ. Medical School 617-432-1550
(Science 27 Feb 98)
-------------------
HERPES VIRUS AS A VIRAL ONCOGENE AND ANGIOGENESIS ACTIVATOR
Kaposi's sarcoma is an ordinarily rare cancer that can be common
in humans with compromised immune systems (for example, in AIDS),
and the herpes viruses are a class of viruses producing the
complex of herpes diseases, some of which are sexually transmit-
ted diseases clinically associated with AIDS. In cell biology,
the term "receptor" denotes a cell surface chemical entity,
usually a protein, that interacts with messenger molecules (e.g.,
hormones) in the extracellular solution. G-proteins are a family
of signal-coupling proteins that act as intermediaries between
activated cell receptors and effectors, for example, the trans-
duction of hormonal signals from the cell surface to the cell
interior. The G-protein is apparently embedded in the cell
membrane with parts exposed on the outside surface and inside
surface. The outside moiety is activated by the first messenger,
and the inside moiety activates the second messenger (which
begins a cascade of signals in the interior of the cell), the G-
protein thus acting as a trans-membrane signal transducer. In the
context of this report, the term "transformation" refers to the
conversion of normal cells into malignant cells exhibiting
uncontrolled growth and loss of functional specialization
(dedifferentiation). Angiogenesis, the origin and development of
blood vessels, is an important consideration in the growth of
cancerous tumors, since the tumor provokes directed angiogenesis
into itself with the end result that the tumor is supplied with
oxygen and nutrients. Without angiogenesis, tumors can attain
only a small size before becoming self-inhibiting. A cytokine is
any substance that promotes cell growth and cell division, and an
inflammatory cytokine is a cytokine involved in the inflammatory
response to tissue injury and infection. As a promoter of cell
growth and division, a cytokine acts as a messenger to cells, and
the transmission of the message requires a binding of the
cytokine molecule to a cytokine-specific receptor on the cell
surface. This receptor is either a protein or a protein complex
or a part of a protein. The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells), and lymphoma is a general
term for a tumor (benign or malignant) of tissue of the lymphatic
system. Bais et al (10 authors at 2 installations, US) report
that signaling by the Kaposi's sarcoma-associated herpes virus G-
protein-coupled receptor leads to cell transformation and tumor
growth, and activates angiogenesis by mechanisms similar to those
produced by inflammatory cytokines. The authors suggest this is
the first demonstration that a Kaposi's sarcoma-associated
herpes virus gene is capable of inducing both transformation and
angiogenesis, and that this evidence strongly supports the idea
that Kaposi's sarcoma-associated herpes virus infection plays a
direct role in Kaposi's sarcoma pathogenesis and lymphoma-
genesis. QY: Enrique A. Mesri
(Nature 1 Jan 98)
-------------------
HERPES VIRUS LINKED TO MULTIPLE SCLEROSIS
In the vertebrate central nervous system, the axons of nerve
cells involved in physiological functions that require rapid
signaling (for example, the neural control of voluntary muscle)
are wrapped in a special sheath called myelin. The myelin sheath
consists of concentric layers of electrically insulating lipid
material, but the sheath is periodically interrupted, and at the
points where the sheath is interrupted so is the electrical
insulation interrupted. The result, predictable from the class-
ical physics of electrical transmission lines and the electrical
parameters of nerve fibers, is that the propagation of an electr-
ical pulse along such nerve fibers occurs at a velocity much
higher than that found in unmyelinated fibers. Multiple sclerosis
is a human disease characterized by the progressive loss of the
myelin of the brain and spinal cord, with the physiological
disruptions to be expected from such loss, considering the
significance of myelin in the functioning of nerve cells. The
herpes viruses are a class of viruses producing the complex of
herpes diseases, and HHV-6 is a recently discovered strain of
herpes virus that apparently causes an infant and early childhood
disease called roseala infantum. Jacobson et al (National
Institutes of Health, US) report that a study of multiple
sclerosis patients (36 patients and 66 controls) revealed that
70% of these patients were infected with the strain of herpes
virus HHV-6. They also report that magnetic resonance imaging
detected numerous myelin lesions in the brain of a deceased
multiple sclerosis patient, and an autopsy revealed HHV-6 in the
lesions but not in the adjoining normal tissues. Some multiple
sclerosis specialists are expressing reservations about the
interpretation of these results, stating it is possible the viral
infection is a consequence rather than a cause of multiple
sclerosis.
QY: Steven Jacobson, National Institute of Neurological Disorders
and Stroke, NIH, Bethesda, MD 20892-0148
(Nature Medicine December 1997)
-------------------
INCREASING U. S. PREVALENCE OF HERPES SIMPLEX VIRAL DISEASE
Genital herpes (also called HSV-2) is a predominantly sexually-
transmitted viral disease caused by the herpes simplex virus. The
disease produces recurrent and often painful skin and internal
lesions, and at the present time there is no cure and only limit-
ed treatment with drugs (e.g., acyclovir). Douglas T. Fleming et
al (7 authors at U.S. Centers for Disease Control and Emory
University, US), examining serological studies of 1976 to 1980,
and new serological studies of 1988 to 1994, report that the
prevalence of HSV-2 infection in the U.S. has increased by 30%
since the late 1970s, and HSV-2 antibody is now detectable in
about 20% of the population over 12 years of age. The authors
suggest that improvements in the prevention of HSV-2 infection
are needed, particularly since such infections, via the genital
ulcers produced, facilitate the transmission of the human immuno-
deficiency virus (HIV), the pathogen in AIDS. QY: Michael E. St.
Louis, CDCP, Mailstop E-02, 1600 Clifton Rd., Atlanta, GA 30333
US (New England J. Med. 16 Oct 97)
-------------------
VIRUSES IN NORMAL CELLS MAY DRIVE GROWTH OF TUMOR CELLS
The idea that viruses are implicated in cancer has existed for
decades, and indeed in a few types of malignancy a related virus
has been identified. But the thinking has always been that if a
virus is implicated in cancer, it is because it invades a cell
type, corrupts the cell's genetic machinery, and the result is a
wild cell that rapidly proliferates. Now a new scheme has
appeared, reported by M. B. Rettig et al (various installations
in Los Angeles, including the University of California Los
Angeles; US). What they have found is that in cases of the human
cancer multiple myeloma, healthy neighboring dendritic cells in
human bone marrow are infected with Kaposi sarcoma-associated
herpes virus, and that this virus is orchestrating the production
by these healthy cells of interleukin-6, a protein which is known
to stimulate myeloma growth. What is striking, is that the virus
does not infect the malignant cells. If these results are
independently confirmed, there will be an intense new interest in
the possibility of viral promotion of various human malignancies.
(Science 20 Jun 97)
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