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Immune Disease C-G
top Candida The last decade has seen the sustained medical importance of opportunistic infections due to different Candida species mainly due to the worldwide increase in the number of immunocompromised patients, who are highly susceptible to opportunistic infections. Meanwhile, the genome sequence of several Candida species has been completed, enabling the detailed investigation of some aspects of their biology with the aid of post-genomic approaches. The basic knowledge gained from these investigations of pathogenic Candida, and related yeasts, can translate into innovations in the development of novel antifungal therapies, original approaches for targeted immuno-interventions, or highly sensitive diagnosis of fungal infections. is a disease
characterized by a population of cells
that grow and divide without respect to normal limits, invade and
destroy
adjacent tissues, and may spread to distant anatomic sites through a
process
called metastasis. These malignant properties of cancers differentiate
them
from benign tumors, which are self-limited in their growth and do not
invade or
metastasize (although some benign tumor types are capable of becoming
malignant). Cancer may affect people at all ages, but risk for the more
common
varieties tends to increase with age. Cancer causes about 13% of all
deaths. Nearly all
cancers are caused by abnormalities in the
genetic material of the transformed cells. These abnormalities may be
due to
the effects of carcinogens, such as tobacco smoke, radiation,
chemicals, or
infectious agents. Other cancer-promoting genetic abnormalities may be
randomly
acquired through errors in DNA replication, or are inherited, and thus
present
in all cells from birth. Complex interactions between carcinogens and
the host
genome may explain why only some develop cancer after exposure to a
known
carcinogen. New aspects of the genetics of cancer pathogenesis, such as
DNA
methylation, and microRNAs are increasingly being recognized as
important. Genetic
abnormalities found in cancer typically affect
two general classes of genes. Cancer-promoting oncogenes are often
activated in
cancer cells, giving those cells new properties, such as hyperactive
growth and
division, protection against programmed cell death, loss of respect for
normal
tissue boundaries, and the ability to become established in diverse
tissue
environments. Tumor suppressor genes are often inactivated in cancer
cells,
resulting in the loss of normal functions in those cells, such as
accurate DNA
replication, control over the cell cycle, orientation and adhesion
within
tissues, and interaction with protective cells of the immune system. Cancer is
usually classified according to the tissue
from which the cancerous cells originate, as well as the normal cell
type they
most resemble. These are location and histology, respectively. A
definitive
diagnosis usually requires the histologic examination of a tissue
biopsy
specimen by a pathologist, although the initial indication of
malignancy can be
symptoms or radiographic imaging abnormalities. Most cancers can be
treated and
some cured, depending on the specific type, location, and stage. Once
diagnosed, cancer is usually treated with a combination of surgery,
chemotherapy and radiotherapy. As research develops, treatments are
becoming
more specific for different varieties of cancer. There has been
significant
progress in the development of targeted therapy drugs that act
specifically on
detectable molecular abnormalities in certain tumors, and which
minimize damage
to normal cells. The prognosis of cancer patients is most influenced by
the
type of cancer, as well as the stage, or extent of the disease. In
addition,
histologic grading and the presence of specific molecular markers can
also be
useful in establishing prognosis, as well as in determining individual
treatments. Chronic fatigue
syndrome (CFS) is one of several names
given to a poorly understood, highly debilitating disorder of uncertain
cause/causes, which is thought to affect approximately 4 per 1,000
adults in
the United States and other countries, and a smaller fraction of
children. The disorder is
marked by chronic mental and physical
exhaustion, often severe, and by other specific symptoms, arising in
previously
healthy and active persons. Despite promising avenues of research,
there
remains no objective assay or pathological finding which is widely
accepted to
be diagnostic of CFS. It remains largely a diagnosis of exclusion, made
on the
basis of patient history and symptomatic criteria, although a number of
tests
exist which can help aid diagnosis. Although there is agreement on the
genuine
threat to health, happiness, and productivity posed by CFS, various
physicians'
groups, researchers, and patient activists champion very different
nomenclature, diagnostic criteria, etiologic hypotheses, and favored
treatments,
resulting in ongoing controversy about nearly all aspects of the
disorder. The
name chronic fatigue syndrome is itself controversial, with some
patient
advocates and other authorities preferring terms such as myalgic
encephalomyelitis ("ME" or "ME/CFS") and post-viral fatigue
syndrome ("PVFS"), which imply specific underlying etiologies or
pathologic processes. Chronic fatigue
syndrome is not the same as
"chronic fatigue”. While fatigue is a common symptom in many illnesses,
CFS is a multi-symptom disease and is relatively rare by comparison.
Definitions (other than the 1991 UK Oxford criteria) require a number
of
features, the most common being severe mental and physical exhaustion
which is
"unrelieved by rest" (according to the 1994 Fukuda definition), and
may be worsened by even trivial exertion (a mandatory diagnostic
criterion
according to some systems). Most diagnostic criteria insist that the
symptoms
must be present for at least six months, and all insist on there being
no other
cause for them: i.e. the symptoms must be idiopathic, not caused by
other
medical conditions such as diabetes, hypothyroidism or anemia. CFS
patients may
report many other symptoms which are not included in all diagnostic
criteria,
including muscle weakness, cognitive dysfunction, hypersensitivity,
orthostatic
intolerance, digestive disturbances, depression, poor immune response,
and
cardiac and respiratory problems. It is unclear if these symptoms
represent
co-morbid conditions or are produced by the same underlying etiology as
CFS
itself. Some cases improve over time, and treatments (though none are
universally accepted) bring a degree of improvement to many others,
though
resolution is rare. CFS occurs more
often, but not exclusively, in women,
for unknown reasons. CFS is most easily diagnosed when formerly active
adults
become ill, and is most commonly diagnosed in young to middle aged
adults,
although it is also reported in children, adolescents and the elderly. The
Epstein-Barr virus (EBV), also called Human
herpesvirus 4 (HHV-4), is a virus of the herpes family (which includes
Herpes
simplex virus and Cytomegalovirus), and is one of the most common
viruses in
humans. Most people become infected with EBV, which is often
asymptomatic but
commonly causes infectious mononucleosis. EBV is named
after Michael Epstein and Yvonne Barr,
who together with Bert Achong, discovered the virus in 1964. Biology On infecting
the B-lymphocyte, the linear virus genome
circularizes and the virus subsequently persists within the cell as an
episome. The virus can
execute several distinct programs of
gene expression which can be broadly categorised as being lytic cycle
or latent
cycle. The lytic cycle
or productive infection results in
staged expression of a host of viral proteins with the ultimate
objective of
producing infectious virions. Formally, this phase of infection does
not
inevitably lead to lysis of the host cell as EBV virions are produced
by
budding from the infected cell. The latent
cycle (lysogenic) programs are those that
do not result in production of virions. A very limited, distinct set of
viral
proteins are produced during latent cycle infection. These include
Epstein-Barr
nuclear antigen (EBNA)-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C,
EBNA-leader
protein (EBNA-LP) and latent membrane proteins (LMP)-1, LMP-2A and
LMP-2B and
the Epstein-Barr encoded RNAs (EBERs). In addition, EBV codes for at
least
twenty microRNAs which are expressed in latently infected cells. From studies of
EBV gene expression in cultured
Burkitt's lymphoma cell lines, at least three programmes exist: EBNA1 only
(group I) EBNA1 + EBNA2
(group II) Latent cycle
proteins (group III). It is also
postulated that a program in which all
viral protein expression is shut off exists. When EBV
infects B-lymphocytes in vitro,
lymphoblastoid cell lines eventually emerge that are capable of
indefinite
growth. The growth transformation of these cell lines is the
consequence of
viral protein expression. EBNA-2, EBNA-3C
and LMP-1 are essential for
transformation while EBNA-LP and the EBERs are not. The EBNA-1 protein
is
essential for maintenance of the virus genome. It is
postulated that following natural infection with
EBV, the virus executes some or all of its repertoire of gene
expression
programmes to establish a persistent infection. Given the initial
absence of
host immunity, the lytic cycle produces large amounts of virus to
infect other
(presumably) B-lymphocytes within the host. The latent
programs reprogram and subvert infected
B-lymphocytes to proliferate and bring infected cells to the sites at
which the
virus presumably persists. Eventually, when host immunity develops, the
virus
persists by turning off most (or possibly all) of its genes, only
occasionally
reactivating to produce fresh virions. A balance is eventually struck
between
occasional viral reactivation and host immune surveillance removing
cells that
activate viral gene expression. The site of
persistence of EBV may be bone marrow. EBV-positive
patients who have had their own bone marrow replaced with bone marrow
from an
EBV-negative donor are found to be EBV-negative after transplantation.
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