Correspondence
may include articles which have only just been pub-
lished in the print journals. However, a question
remains to be answered: Is the number of down-
loads a reliable measure of research quality?
In order to find an answer to this question,
firstly, we took TOP25 Hottest Articles of Decem-
ber 2006 in ‘‘Journal of Chromatography A’’, as
the first set. Similarly, another set consisted of
25 articles were selected as the non-Hottest, each
of which was corresponded to the members of the
first set. All these have become available online at
different months of 2006. There is a possibility that
investigators judged based on the number of cita-
tions. Consequently, some authors may try to
self-cite to promote a scholarly reputation [1]. To
avoid the influence of self-citation in the evalua-
tion of the articles, citation of each article (also
available at ScienceDirect alerting service) were
considered and cases of self-citation were not
involving in research evaluation process. Analysis
of the data was performed by using independent
samples t-test to compare the mean frequencies
of citations of two distinct groups of articles.
The results of statistical test (t-test) revealed
that citation means frequencies (1.52 for Hottest
and 0.76 for non-Hottest article groups) showed
doi:10.1016/j.mehy.2007.01.007
What is the real cause of glaucoma?
Glaucoma can be defined as an optic nerve dis-
ease with typical morphological and functional
changes [1]. There are many risk factors associ-
ated with this neuropathy such as central corneal
thickness (CCT), age, race, sex, intraocular
pressure (IOP), optic nerve changes, refractive
error, systemic diseases, family history and
trauma [2].
There are many observations, which can hardly
be explained by direct effect of increasing IOP.
One of them is that as many as 1/6 of the patients
with glaucomatous damage do not have increased
IOP even with repeated testing. Also, Ocular hyper-
tension is 10 times more common than glaucoma-
tous neuropathy. Another conflict is that the
presence and the progression of glaucomatous
damage are weakly related to the level of IOP
[1]. These conflicts led us to find another factor
more than IOP to describe development of glau-
coma. CCT and scleral thickness have a moderately
459
significant difference (2.212 of t-value) between
two groups, (p-value = 0.015). Positive t-value re-
sult means that more citations have been done to
Hottest Articles at the same period, compared to
the non-Hottest group. In conclusion, our investiga-
tion showed that more downloads at a limited per-
iod of time is an indicator of more citations to the
article in a long-term interval.
Reference
[1] Daya S. Self-citation and the journal impact factor. Evi-
dence-based. Obstet Gynecol 2004;6:159–60.
Samad Jahandideh *
Parviz Abdolmaleki
Ebrahim Barzegari Asadabadi
Department of Biophysics,
Faculty of Science,
Tarbiat Modares University,
P.O. Box 14115/175,
Tehran,
Iran
* Tel.: +98 21 88950325.
E-mail address: jahandideh@modares.ac.ir
(S. Jahandideh).
positive correlation [2]. So, we use scleral thick-
ness instead of CCT below.
The incidence of glaucomatous damage in the
same IOP conditions varies between different
races and sexes [1] therefore, scleral thickness
and internal radius of the eye globe which also de-
pend on race and sex [3,4] can be considered as
the factors that are responsible for glaucoma in
theses conditions.
In the eye globe as an idealized spherical shell,
stress depends on IOP, inner radius of the eye
globe, and scleral thickness [5].
Therefore, in contrast to old theories, which
consider direct effect of increased IOP as leading
cause of glaucoma, stress is the main responsible
factor for glaucomatous damage and increasing
IOP acts just as one of the determinant factors of
glaucoma. Stress can develop glaucomatous dam-
age in two ways: stress directly obstruct the retinal
vessels and develop glaucoma by ischemic damage.
460
Also, stress by inducing strain (tissue deformation
in response to load) can deform and interrupt the
retinal layers, which end in glaucoma too.
In conclusion, a series of factors together deter-
mine whether an individual will be affected with
glaucoma or not. These factors include IOP, scleral
thickness, radius of the eye globe, and optic nerve
head compliance against increased stress. These
factors differ between different individuals. So risk
of glaucoma is different between them. Our
hypothesis explains the existence of normal-pres-
sure (tension) glaucoma. It presents a better meth-
od for screening of glaucoma and new modalities
for glaucoma treatment.
References
[1] Flammer J, Orgül S. Optic nerve blood-flow abnormalities in
glaucoma. Prog Retin Eye Res 1998;17:267–89.
[2] Mehdizadeh AR, Hoseinzadeh A, Fazelzadeh A. Central
corneal thickness as a risk factor for glaucoma. Med
Hypotheses [in press].
doi:10.1016/j.mehy.2007.01.004
Innate immune system: Specific or non-specific?
Mammalian immune system has two arms: adaptive
and innate. Adaptive immunity consists of T and B
cells. Innate immune system includes more cells:
natural killer (NK) cell, dendritic cell (DC), macro-
phage and neutrophil. Since 15 years ago, some
receptors have been found in innate immune sys-
tem such as toll-like receptors (TLRs) [1], nucleo-
tide-binding oligomerization domains (NODs) [2]
and C-type lectins (e.g. DC-SIGN) [3] which are
named pattern-recognition receptors (PRRs) and
detect specific molecules of pathogens that are
called pathogen-associated molecular patterns
(PAMPs). Thirteen members of TLRs, as the main
PRRs, have been characterized which recognize
different PAMPs and modulate immune response
in different ways. To compare the properties of
TLRs, with TCRs and immunoglobulins, we mention
the following similarities along with some evi-
dence. TLR4 recognizes typical lipopolysaccharide
(LPS) of E. coli but atypical LPS produced by Por-
phyromonas gingivalis is recognized by TLR2 [4].
So, different variants of the same PAMP can be rec-
ognized by different TLR molecules and conse-
quently distinct responses are elicited while TCRs
and immunoglobulins can distinguish between epi-
Correspondence
[3] Aghaian E, Choe JE, Lin S, Stamper RL. Central corneal
thickness of Caucasians, Chinese, Hispanics, Filipinos, Afri-
can Americans, and Japanese in a glaucoma clinic. Ophthal-
mology 2004;111:2211–9.
[4] Hahn S, Azen S, Ying-Lai M, Varma R, et al. Central corneal
thickness in Latinos. Invest Ophthalmol Vis Sci 2003;44:
1508–12.
[5] Bellezza AJ, Hart RT, Burgoyne CF. The optic nerve
head as a biomechanical structure: initial finite element
modeling. Invest Ophthalmol Vis Sci 2000;41:2991–
3000.
Ali Reza Mehdizadeh *
Amin Hoseinzadeh
Afsoon Fazelzadeh
Department of Medical Physics,
School of Medicine,
Mashad University of Medical Sciences,
Mashad,
Iran
* Tel.: +98 9155103108.
E-mail address: alireza.mehdizadeh@gmail.com
(A.R. Mehdizadeh).
topes which differ in even one amino acid. Combi-
nation of different TLR’s can result in new
specificity for a new ligand. For example, combina-
tion of TLR1 and TLR2 (TLR1/2) identifies a syn-
thetic bacterial lipopeptide, PAM3CSK4 whereas
TLR2/6 recognize a synthetic mycoplasmal lipo-
peptide, MALP-2. PAM3CSK4 contains triacylated
cysteinyl residue at the N-terminus, whereas the
cysteinyl residue in MALP-2 is only diacylated [5].
Immunoglobulines, also use the same approach
for creating diversity. Light chains and heavy
chains of different antibodies (with different spec-
ificities) may combine and recognize a new anti-
gen. Recently, it has been shown that TLR3, TLR7
and TLR9 which recognize nucleic acids are local-
ized to intracellular compartments. The purpose
of intracellular localization is not clear but there
are some data demonstrating that intracellular
localization of TLR9 is not required for ligand rec-
ognition; instead, is critical in discriminating be-
tween self and non-self nucleic acid [6]. Negative
selection in adaptive immune system leads in dele-
tion of T and B cells which can identify endogenous
proteins. Recently, a profilin-like protein was
found in Toxoplasma gondii, as TLR11 ligand [7].